U.S. Route 51 (US 51) in the U.S. state of Illinois, is a main north–south artery that runs from the Ohio River north to the Wisconsin border, a distance of 415.95 miles (669.41 km).

US 51 enters Illinois from Kentucky at Cairo, Illinois. The highway heads northbound to Mounds, near Cairo, and begins to overlap Interstate 57 (I-57), following it for 24 miles (39 km) to Dongola, before splitting and heading north. The highway remains two lanes wide from Dongola to Assumption with the exception of a 10-mile (16 km) section between Centralia and I-64.

Past Assumption, US 51 becomes an expressway to Decatur. In Decatur, US 51 follows I-72 to bypass the city. US 51 leaves I-72 after eight miles (13 km), and it heads north to Bloomington–Normal as an expressway. At Bloomington–Normal, US 51 follows I-74 for a mile, then I-55 for seven miles (11 km), before following I-39 for 140 miles (230 km).

US 51 follows I-39, intersecting I-80 and I-88 along the way. The highway also follows US 20 south of Rockford (while still following I-39). I-39/US-51 join I-90, making US 51 one of the few toll highways in Illinois that is a U.S. Highway. US 51 exits I-39/I-90 just a mile south of the Wisconsin state line. Then US 51 follows Illinois Route 75 (IL 75) west to the intersection of IL 251, and then turns north through South Beloit, Illinois to enter Wisconsin.

US 51 was established in Illinois in the 1920s. Over the years, it became a heavily traveled highway, often experiencing many accidents, particularly in the northern half of the state. This highway gained the moniker of "Killer 51". As a result of these problems, Illinois pushed for a new four lane highway along the corridor. One was proposed in the 1960s and 1970s as part of a proposed supplemental freeway system, but only the area between Rockford and Decatur was given a high priority.

In the 1980s and early 1990s, US 51 was rebuilt to Interstate standards between Rockford and Bloomington–Normal on a new alignment. This new highway became Interstate 39, and US 51 was rerouted onto it. In addition, north of Rockford, US 51 was rerouted onto the existing I-90 segment between South Beloit and Cherry Valley. Most of the old highway became IL 251.

South of Bloomington–Normal to Decatur, US 51 remained largely on the original alignment, and it was expanded to an expressway. In the 2000s, the expressway was continued southward from Decatur to Assumption, Illinois.

County	Location	mi	km	Exit	Destinations	Notes
Alexander	Cairo	0.0	0.0		US 51 south / US 60 east / US 62 east – Wickliffe	Continuation into Kentucky
		0.2	0.32		US 60 west / US 62 west to I-57 south – Charleston	Northern end of US 60/US 62 concurrency
		4.5	7.2		IL 37 north – Mound City IL 3 north	Southern end of IL 3 concurrency; southern termini of IL 3 and IL 37
		5.3	8.5	1	I-57 south / IL 3 north – Olive Branch, Sikeston, MO	Northern end of IL 3 concurrency; southern end of I-57 concurrency
Pulaski	​	11.4	18.3	8	Mounds Road
	​	21.4	34.4	18	Ullin Road
Union	Dongola	28.2	45.4	24	Dongola Road
		28.8	46.3	25	I-57 north – Chicago	Northern end of I-57 concurrency; Northbound exit and southbound entrance
	Anna	36.0	57.9		IL 146 – Jonesboro, Vienna
Jackson	Carbondale	55.0	88.5		IL 13 – Murphysboro, Marion
	De Soto	61.3	98.7		IL 149 – Murphysboro, Hurst
Perry	Du Quoin	72.4	116.5		IL 14 east – Christopher	Western terminus of IL 14
		75.5	121.5		IL 152 west – Pyatts	Eastern terminus of IL 152
	Sunfield	80.4	129.4		IL 154 – Red Bud, Sesser
Washington	Ashley	98.0	157.7		IL 15 west – East St. Louis	Western end of IL 15 concurrency
		100.9	162.4		IL 15 east – Mount Vernon	Eastern end of IL 15 concurrency
	Richview	105.7	170.1		I-64 – Mount Vernon, East St. Louis	I-64 exit 61
	Irvington	109.6	176.4		IL 177 west – Belleville	Western terminus of IL 177
Jefferson	No major junctions
Marion	Centralia	116.2	187.0		IL 161 – New Baden, Kell
	Sandoval	122.7	197.5		US 50 west – Carlyle	Western end of US 50 concurrency
		123.0	197.9		US 50 east – Salem	Eastern end of US 50 concurrency
Fayette	Vandalia	146.9	236.4		US 40 east / IL 185 east – Bluff City	Eastern end of US 40/IL 185 concurrency
		148.5	239.0		US 40 west / IL 185 west – Taylor Springs, Mulberry Grove	Western end of US 40/IL 185 concurrency
		148.7	239.3		I-70 – Effingham, St. Louis	Exit 63 on I-70
Shelby	No major junctions
Christian	Pana	178.1	286.6		IL 16 west – Hillsboro	Western end of IL 16 concurrency
		178.6	287.4		IL 29 north – Taylorville	Southern terminus of IL 29
	​	180.2	290.0		IL 16 east – Shelbyville	Eastern end of IL 16 concurrency
Shelby	No major junctions
Macon	​	207.3	333.6		Elwin, Mt Zion	Northbound exit, southbound entrance
		210	340		Decatur, Elwin, Mt Zion	Interchange
	​	211.2	339.9		IL 48 – Taylorville, Decatur
	Harristown	214.7	345.5	133	I-72 west / US 36 – Springfield, Decatur	Southern end of I-72 concurrency; signed as exits 133A (east) and 133B (south)
	Decatur	219.2	352.8	138	IL 121 – Decatur, Lincoln
		222.2	357.6	141	I-72 east – Champaign, Urbana, Decatur	Northern end of I-72 concurrency
DeWitt	Clinton	237.9	382.9		US 51 Bus. north – Clinton
		239.5	385.4		IL 54 – Springfield, Clinton
		240.0	386.2		IL 10 – Lincoln, Clinton
		242.0	389.5		US 51 Bus. south – Clinton
McLean	Heyworth	251.9	405.4		US 136 – McLean, Rantoul
	​	260.5	419.2	135	US 51 Bus. (Main Street) – Bloomington I-74 east – Champaign	Southern end of I-74 concurrency
	​	262.2	422.0	157A	I-55 south – St. Louis, Springfield	Southern end of I-55 concurrency
	Bloomington	262.4	422.3	157B	I-55 BL north (Veterans Parkway)	Signed as exit 134B (north) southbound
		265.5	427.3	160	US 150 / IL 9 (Market Street) – Pekin
	​	269.1	433.1	163	I-74 west – Peoria	Northern end of I-74 concurrency
	​	270.3	435.0	—	I-55 north – Chicago I-39 north	Northern end of I-55 concurrency; southern end of I-39 concurrency; southern terminus of I-39; I-55 exit 154
	​	272.1	437.9	2	US 51 Bus. south – Bloomington, Normal
	Hudson	275.2	442.9	5	CR 12 (Franklin Street) – Hudson
	​	278.3	447.9	8	IL 251 north / CR 8 (Lake Bloomington Road) – Kappa	Southern terminus of IL 251
Woodford	El Paso	284.9	458.5	14	US 24 – El Paso, Peoria
	Woodford	292.9	471.4	22	IL 116 – Peoria, Pontiac
	Minonk	297.5	478.8	27	Minonk
Marshall	Wenona	305.6	491.8	35	IL 17 – Lacon, Wenona
LaSalle	Lostant	312.2	502.4	41	IL 18 – Henry, Streator
	Tonica	319.2	513.7	48	Tonica
	​	322.3	518.7	51	IL 71 – Hennepin, Oglesby
	​	323.0	519.8	52	IL 251 – Peru, LaSalle
	Oglesby	324.4	522.1	54	Oglesby
	Illinois River	326.5	525.5	Abraham Lincoln Memorial Bridge
	La Salle	327.3	526.7	57	US 6 – LaSalle, Peru, Ottawa
	​	329.6	530.4	59	I-80 – LaSalle, Peru, Chicago, Des Moines	Signed as exits 59A (east) and 59B (west); I-80 exit 79
	Troy Grove	336.8	542.0	66	US 52 – Troy Grove
	Mendota	342.7	551.5	72	US 34 – Mendota, Earlville
Lee	Paw Paw	353.1	568.3	82	Paw Paw
	​	357.9	576.0	87	US 30 – Sterling, Rock Falls, Aurora
	Steward	363.9	585.6	93	Steward
Ogle	Rochelle	368.0	592.2	97	I-88 Toll / IL 110 (CKC) (Ronald Reagan Memorial Tollway) – Moline, Rock Island, Chicago	Signed as exits 97A (east) and 97B (west); I-88 exit 78
		370.1	595.6	99	IL 38 / Lincoln Highway – DeKalb, Rochelle
	Lindenwood	375.1	603.7	104	IL 64 – Sycamore, Oregon
	Monroe Center	381.6	614.1	111	IL 72 – Genoa, Byron
Winnebago	​	386.1	621.4	115	Baxter Road
	Rockford	390.2	628.0		US 20 west (Rockford Bypass) – Freeport, Rockford	Southern end of US 20 concurrency
	Cherry Valley	392.7	632.0	122A	US 20 east – Belvidere	Northern end of US 20 concurrency
		392.7	632.0	122B	Harrison Avenue
		393.4	633.1		I-90 Toll east (Jane Addams Memorial Tollway) – Chicago	Southern end of I-90 concurrency; I-39/US 51 uses I-90's exit numbers from here north; exit 17 on I-90
	Rockford	395.1	635.9	15	US 20 Bus. (State Street)	Last free exit northbound
		398.4	641.2	12	Riverside Boulevard	Toll on northbound exit and southbound entrance
	Machesney Park	401.9	646.8	9	IL 173 (West Lane Road) – Machesney Park	Toll on northbound exit and southbound entrance
	Rockton	407.3	655.5	South Beloit Toll Plaza
	South Beloit	408.1	656.8	3	CR 9 (Rockton Road)	Last free exit southbound
		414.0	666.3	1	I-39 north / I-90 west – Madison IL 75 east (Manchester Road)	Northern end of I-39/I-90 concurrency; southern end of IL 75 concurrency
		415.6	668.8		IL 75 west (Gardner Street) / IL 251 south (North 2nd Street) – Freeport, Rockford	Northern end of IL 75 concurrency; northern terminus of IL 251
		415.95	669.41		US 51 north (Dearborn Street) – Beloit	Continuation into Wisconsin
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus       Incomplete access        Tolled

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U.S. Route 51
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