Leaving the Akron area, I-76 again heads through rural areas, crossing Portage County and entering Mahoning County. West of Youngstown, the freeway intersects the Ohio Turnpike and I-80 via a double trumpet interchange. I-76 joins the Ohio Turnpike heading southeast toward Pittsburgh while I-80 exits the Turnpike and continues east toward Youngstown. The Ohio Turnpike carries I-76 until the Pennsylvania border, where I-76 joins the Pennsylvania Turnpike.

From the Ohio border, the Pennsylvania Turnpike carries I-76 into and across most of Pennsylvania, bypassing Youngstown, Ohio, to the south and Pittsburgh to the north. There is a free interchange with US 19 and I-79 near Wexford. At one point, I-76 used to begin in Pittsburgh on a route that was signed as I-376 around the 1970s. It intersects with this highway in Monroeville.

From New Stanton to Breezewood, I-76 is concurrent with I-70. In this section are the bypass (built in the 1960s) of the Laurel Hill Tunnel, then the still-in-use Allegheny Mountain Tunnel in a relatively unpopulated section of South Central Pennsylvania, and then an indirect connection with I-99 in Bedford. The highway also passes through the Somerset Wind Farm and is the closest Interstate Highway to the Flight 93 National Memorial in Shanksville.

At Breezewood, I-70 exits the turnpike (making use of a short stretch of the old alignment of the Pennsylvania Turnpike), while I-76 bypasses the Rays Hill and Sideling Hill tunnels along a new alignment built in the 1960s. The major features of this section are more mountains with the Tuscarora Mountain Tunnel and then a double tunnel (Kittatinny/Blue Mountain) prior to Pennsylvania Route 997 (PA 997) near Shippensburg. I-76 intersects I-81 (indirectly) in Carlisle then I-83 and I-283 near Harrisburg, bypassing Harrisburg to the south. The Susquehanna River Bridge is a six-lane bridge that was constructed in 2003 using precast segments that replaced an older bridge across the Susquehanna River. In Morgantown, I-176 provides a connection north to Reading. At Valley Forge, I-76 diverges toward Philadelphia, but the turnpike (as I-276) bypasses it to the north.

At Valley Forge, northwest of Philadelphia, I-76 leaves the Pennsylvania Turnpike to run into Philadelphia on the Schuylkill Expressway (while the Pennsylvania Turnpike continues east as I-276). Immediately after exiting the turnpike, I-76 interchanges with the US 202 and US 422 freeways near King of Prussia. I-76 later crosses I-476 near Conshohocken and begins running along the southwest shore of the Schuylkill River. I-76 then enters the city/county limits of Philadelphia where interchanges provide access to US 1 (Roosevelt Expressway) and the Vine Street Expressway (I-676); the latter runs through Center City while I-76 bypasses to the south.

After the Grays Ferry Avenue exit near University City, I-76 crosses the Schuylkill Expressway Bridge to go toward the South Philadelphia Sports Complex near Lincoln Financial Field, Wells Fargo Center, and Citizens Bank Park.

The last interchange before the Walt Whitman Bridge over the Delaware River into New Jersey is with I-95. Some of the ramps involve traffic signals, as the ramps to I-95 were retrofitted into an existing interchange when I-95 was built, and the tollbooth for the bridge lies west of the crossing of the two roads.

Just after crossing the Delaware River on the Walt Whitman Bridge, I-76 turns south and becomes the North–South Freeway, which carries I-676 north to Downtown Camden; the unsigned Route 76C connector runs east to US 130 and Route 168. The exit numbers in New Jersey are backward, running from east to west. Though signed eastbound toward Atlantic City, the route ends near Gloucester City in western Camden County at an interchange with I-295.

From the exit for I-676 to the end, I-76 originally had local–express lanes in both directions; the barriers in both directions, however, have been removed due to rebuilding of the I-295, I-76, and Route 42 interchange. I-76 ends at an interchange with I-295 on the Mount Ephraim–Bellmawr town line. The road becomes Route 42, continuing south on the North–South Freeway and then feeding into the A.C. Expressway to Atlantic City. While the South Jersey Transportation Authority (which owns the A.C. Expressway) is not against the idea of making the freeway section of Route 42 and the A.C. Expressway an eastern extension of I-76, they feel that making the change without a compelling reason would only add to motorists' confusion in southern New Jersey.

The majority of I-76 along the Pennsylvania Turnpike includes the first long-distance rural freeway in the U.S.; the Ohio Turnpike and Schuylkill Expressway are also pre-Interstate freeways. By 1955, the section of that route from west of Youngstown to Center City, was included in the planned Interstate Highway System, as was present I-76 from west of Youngstown to Akron. (Some early plans called for a new freeway along SR 14 to the Pennsylvania state line; it is unclear when the proposed route was shifted to the turnpikes.)

In 1957, the route from Cleveland east to Harrisburg, running roughly along the SR 14 corridor in Ohio and the turnpike in Pennsylvania, was labeled I-80, and the rest of the route from Harrisburg to Philadelphia was assigned I-80S. (I-80N would have run from Harrisburg to New York City.) I-78 was assigned to a route from Norwalk, paralleling SR 18 through Akron to Youngstown and turning south there to end at the planned I-80.

The 1957 numbering, however, was drawn on a map from 1947, which did not include several changes that had been approved, specifically the Keystone Shortway across Pennsylvania. (The route in that corridor ran further north, along US 6, and was numbered I-84.) Thus, the final numbering, approved in 1958, assigned I-80 to the Norwalk–Youngstown route to reach the Keystone Shortway. The former alignment through Cleveland became I-80N; the turnpike was still not assigned a number from near Elyria (where I-80N and I-90 would split from it) to west of Youngstown. The route from west of Youngstown to Philadelphia was assigned I-80S, and extended east to I-295 in New Jersey when auxiliary Interstates were assigned in 1959. (The planned I-80N in Pennsylvania became I-78.) Initial spurs of I-80S were I-180 (now I-176), I-280 (now I-276), I-480 (now I-476), and I-680 (now I-676, though it swapped with I-76 in 1972).

I-80 was realigned in Ohio by 1962, largely taking over former I-80N, which ran through Cleveland, joining the turnpike southwest of Cleveland. However, while I-80N was planned to split from I-80 near Kent and run northwest to Cleveland along SR 14, the new alignment of I-80 used the turnpike between the crossing west of Youngstown and the crossing with SR 14 at Streetsboro. The former I-80 from near Youngstown west to Akron became part of I-80S, as did a new alignment (already built as US 224) from Akron west to I-71 east of Lodi; the rest of proposed I-80 west to near Norwalk (which would have crossed I-71 near Medina) was removed from the Interstate Highway System. I-80 was moved to the turnpike between Streetsboro and southwest of Cleveland c. 1971; the old route became I-480.

On April 16, 1963, due in part to the extension of I-79 south from Greater Pittsburgh, Pennsylvania proposed a partial renumbering. A new number, tentatively designated I-76, would run from Downtown Pittsburgh east on what was then I-70 (I-70S bypassed Pittsburgh to the south on what is now I-70) to the Pennsylvania Turnpike at Monroeville, and then east along the remainder of I-80S to I-295. I-80S would remain on the section of turnpikes from west of Youngstown to Monroeville. This was approved February 26, 1964, and included the renumbering of all I-X80 spurs to I-X76.

On June 29, 1970, a renumbering was approved in the Pittsburgh area, with the main effect being rerouting I-79 to bypass Pittsburgh to the west on the former I-279. I-279 was moved to the former I-79 north of downtown, and the former I-79 from downtown southwest to new I-79 became a western extension of I-76. (It was then that I-876 was designated for former I-479.) A realignment and extension of I-76 into Ohio, taking over the rest of I-80S to I-71 east of Lodi, was approved January 11, 1972. The former I-76 from Monroeville west into Downtown Pittsburgh became I-376, and I-279 was extended southwest from downtown along former I-76 to I-79. (I-876 was renumbered to I-579 then.) Signs in Ohio were changed September 1, 1972; the old I-80S signs remained for about a year.

On August 29, 1972, a swap of I-76 and I-676 in Philadelphia and Camden was approved. I-76 had been routed along the Vine Street Expressway and Ben Franklin Bridge (now I-676) through Center City, while I-676 used the Schuylkill Expressway and Walt Whitman Bridge to bypass downtown to the south. The switch was made because of delays in building the Vine Street Expressway, better interchange geometry at the splits, and that the Ben Franklin Bridge ends in city streets, rather than in expressway grade.

The renumbering of a Philadelphia Interstate to I-76 in the years leading up to the Bicentennial Celebration of the 1776 signing in Philadelphia of the Declaration of Independence gives rise to the question of the highway number being an intentional tribute to the spirit of 1776. U.S. Department of Transportation research into federal documentation of the I-76 renumbering found no evidence of this being intentional.

In Ohio and Pennsylvania, the routes are composed mostly of turnpikes with the exceptions in east-central Ohio and the Delaware Valley. The exit numbers on the turnpike portions in Ohio follow the mileage markers for the Ohio Turnpike.

County	Location	mi	km	Exit	Destinations	Notes
Medina	Westfield Township	0.00	0.00		US 224 west – Napoleon	Continuation west; west end of US 224 overlap
				1	I-71 – Columbus, Cleveland, Cincinnati	Signed as exits 1A (south) and 1B (north) westbound; I-71 exits 209A-B
	Seville	2.32	3.73	2	SR 3 – Medina, Seville
	Wadsworth	7.72	12.42	7	SR 57 – Rittman, Medina
		9.76	15.71	9	SR 94 – North Royalton, Wadsworth
		11.71	18.85	11	SR 261 – Norton, Wadsworth
Summit	Norton	13.32	21.44	13	SR 21 – Massillon, Cleveland	Signed as exits 13A (south) and 13B (north)
		14.65	23.58	14	Cleveland–Massillon Road
		16.19	26.06	16	Barber Road
	Barberton	17.53	28.21	17	State Street to SR 619 (East Avenue / Wooster Road)	Former partial diamond interchange; reconstructed to a full diamond interchange to increase the distance from I-277/Kenmore Leg interchange
		17.83	28.69		SR 619 (East Avenue / Wooster Road) – Barberton	Westbound entrance via State Street
	Akron	18.62	29.97	18	I-277 east / US 224 east – Mogadore	Westbound exit and eastbound entrance; east end of US 224 overlap; I-277 exit 1
		19.04	30.64	19	Battles Avenue / Kenmore Boulevard
		20.45	32.91	20	I-77 north – Cleveland	Eastbound exit and westbound entrance; west end of I-77 overlap; exit number not signed westbound
		20.79	33.46	21A	East Avenue	Westbound exit closed from January 2022 to December 2023 for reconstruction
		21.59	34.75	21B	Lakeshore Boulevard, Bowery Street	Eastbound exit and entrance
		21.73	34.97	21C	SR 59 east – Downtown	Eastbound signage
		21.77	35.04		To SR 59 east / Dart Avenue	Westbound signage
		22.39	36.03	22	Main Street, Broadway Street – Downtown	Was exit 22A before Wolf Ledges/Grant Street exit was removed
		22.79	36.68	22B	Wolf Ledges, Grant Street	Closed June 14, 2017
		23.57	37.93	23	I-77 south / SR 8 north – Canton, Cuyahoga Falls, Cleveland	East end of I-77 overlap; signed as exits 23A (north) and 23B (south)
		23.83	38.35	24A	Inman Street, Johnston Street	Former westbound exit only; closed November 7, 2021
		24.34	39.17	24	Arlington Street	Westbound signage; was exit 24B before Inman Street/Johnston Street exit was removed
		24.71	39.77		Arlington Street, Kelly Avenue	Eastbound signage
		25.00	40.23	25A	SR 241 (Innovation Way)	Signed as exit 25 westbound
		25.67	41.31	25B	Brittain Road	Eastbound exit and westbound entrance
		26.11	42.02	26	SR 18 (East Market Street)	Access to Mogadore Road (former SR 526)
	Springfield Township	27.35	44.02	27	Gilchrist Road, Canton Road to SR 91
	Tallmadge	29.00	46.67	29	SR 532 – Mogadore, Tallmadge
Portage	Brimfield Township	31.31	50.39	31	CR 18 (Tallmadge Road)
		33.04	53.17	33	SR 43 – Kent, Hartville
	Rootstown Township	38.53	62.01	38	SR 5 east / SR 44 – Ravenna	Signed as exits 38A (south) and 38B (north) eastbound
	Edinburg Township	43.07	69.31	43	SR 14 – Alliance, Ravenna
	Palmyra Township	48.58	78.18	48	SR 225 – Alliance
Mahoning	Milton Township	54.04	86.97	54	SR 534 – Lake Milton, Newton Falls
	Jackson Township	57.25	92.13	57	To SR 45 / Bailey Road – Warren
		59.85	96.32	218 (WB) 219 (EB)	I-80 / Ohio Turnpike west – Toledo, Youngstown
					CR 18 (Mahoning Avenue)	Westbound exit and eastbound entrance
	Overlap with Ohio Turnpike
	Springfield Township	82.12	132.16		I-76 east / Penna Turnpike east – Pittsburgh	Continuation into Pennsylvania
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus       Closed/former       Incomplete access        Tolled

The entire route is in Camden County.

Location	mi	km	Exit	Destinations	Notes
Delaware River	3.08	4.96	–	I-76 west (Schuylkill Expressway) – Philadelphia	Continuation into Pennsylvania
			Walt Whitman Bridge (westbound toll in Pennsylvania)
Camden	2.30– 2.21	3.70– 3.56	354 (EB) 2 (WB)	I-676 north to US 130 north / Route 168 south – Camden, Gloucester, Benjamin Franklin Bridge	Access to US 130/Route 168 via Route 76C; no westbound access to US 130/Route 168
Gloucester City	1.15– 0.76	1.85– 1.22	1D-C	US 130 – Collingswood, Brooklawn, Westville	Signed as exits 1D (north) and 1C (south); no eastbound access to US 130 north
Bellmawr	0.00	0.00	1B-A	I-295 to N.J. Turnpike – Trenton, Delaware Memorial Bridge	Signed as exits 1B (north) and 1A (south); no westbound access to I-295 south; exits 26-27 on I-295
			–	Route 42 south to A.C. Expressway east – Atlantic City	Continuation south
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Closed/former       Incomplete access        Tolled

• I-176 runs north from I-76 at Morgantown, Pennsylvania, to US 422 outside of Reading, Pennsylvania.
• I-276 runs east from I-76 at Valley Forge, Pennsylvania, along the Pennsylvania Turnpike to I-95 in Bristol Township, Pennsylvania.
• I-376 runs west from I-76 at Monroeville, Pennsylvania, through Pittsburgh, Pennsylvania, becomes a toll road northwest of the airport, intersects I-76 again, and terminates at I-80 in Sharon, Pennsylvania.
• I-476 begins at I-95 near Chester, Pennsylvania, and heads north, crossing I-76 near Conshohocken, Pennsylvania, and I-276 near Plymouth Meeting, Pennsylvania. From there it continues north on the Pennsylvania Turnpike Northeast Extension to I-81 at Clarks Summit, Pennsylvania, north of Scranton, Pennsylvania. I-476 is the longest auxiliary Interstate.
• PA 576 is a planned, partially completed, southern bypass of Pittsburgh, Pennsylvania, though it could become I-576.
• I-676 is a loop through Center City, Philadelphia, and Camden, New Jersey, crossing the Benjamin Franklin Bridge. It runs through several traffic signals in Philadelphia, Pennsylvania, in violation of Interstate Highway standards.
• I-876 was the number for present I-579 in Pittsburgh, Pennsylvania, in the early 1970s.
• Interstate 76 Alternate (I-76 Alt.) is an incident bypass route located in Summit County, Ohio, that runs along SR 21 and I-77 between Norton, Ohio, and Akron, Ohio.
• Interstate 76 Connector (I-76 Conn.) is an unsigned business route located in Camden, New Jersey, that runs from the I-76 and I-676 interchange to Route 168. It interchanges US 130 before reaching its eastern terminus.

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Wikimedia Commons has media related to Interstate 76 (Ohio–New Jersey).

• Geographic data related to Interstate 76 (Ohio–New Jersey) at OpenStreetMap
• Interstate 76 (Eastern) at Interstate-Guide.com Archived October 18, 2012, at the Wayback Machine
• The Roads of Metro Philadelphia: Interstate 76 - New Jersey
• New Jersey Roads - I-76
• I-76 New Jersey at AARoads.com