State Route 65 (SR 65) is a north–south highway in western Ohio. Its southern terminus is at State Route 47 near Sidney, and its northern terminus is at its interchange with Interstate 280 in Toledo. From south to north, the route passes through the cities of Jackson Center, Uniopolis, Lima, Columbus Grove, Ottawa, Leipsic, Belmore, McClure, Grand Rapids, Perrysburg, Rossford, and Toledo.

Route 65 parallels the south bank of the Maumee River for its northernmost 32 miles, from east of Napoleon to Toledo.

State Route 65 is an original state highway. Its original southern terminus was at State Route 15 in Ottawa, and it crossed the Maumee River near Liberty Center, continuing northward to Delta and terminating at the Michigan state line.

In 1931, the route's northern terminus was moved to downtown Toledo along its current route. Most of its former route north of the Maumee River is now that of State Route 109. From 1931 until 1989, State Route 65 did not cross the Maumee River. Until 1964, its route from Perrysburg to Toledo was superseded by U.S. Route 23.

In 1938, State Route 65's southern terminus was extended to its current terminus. It replaced the now defunct State Routes 33 and 318.

In 1989, when U.S. Route 223 was truncated back to Sylvania, State Route 65 was extended along its former route (along with State Route 51) across the Maumee on the Anthony Wayne Bridge. State Route 51 took U.S. Route 223's route on Monroe Street, while State Route 65 took the route of Summit Street from there to Interstate 280.

In June, 2007, the Veterans' Glass City Skyway opened, taking Interstate 280 across the Maumee. Subsequently, State Route 65 was rerouted onto the Robert Craig Memorial Bridge, the former crossing of Interstate 280 across the river, the week after the new bridge opened, ending at the former Front Street interchange.

County	Location	mi	km	Destinations	Notes
Shelby	Salem Township	0.00	0.00	SR 47 – Sidney, Bellefontaine
	Jackson Township	3.21	5.17	SR 119 west to I-75 – Anna	Eastern terminus of SR 119
	Jackson Center	6.21	9.99	SR 274 (Pike Street)
Auglaize	Clay Township	10.37	16.69	SR 720 east / CR 100 (Santa Fe New Knoxville Road)	Western terminus of SR 720
	Clay–Union township line	14.48	23.30	US 33 east / Boundary Road – Lakeview	Southern end of US 33 concurrency
		16.53	26.60	US 33 / Walnut Street west – Wapakoneta	Northern end of US 33 concurrency
	Uniopolis	19.72	31.74	SR 67 (Ohio Street)
Allen	Lima–Perry Township municipal line	26.37– 26.45	42.44– 42.57	I-75 – Toledo, Dayton	Exit 122 (I-75)
	Lima	29.15	46.91	SR 117 east / SR 309 east (Elm Street) / Pine Street	Southern end of SR 117 / SR 309 concurrencies
		29.37	47.27	SR 117 west (Elm Street) / Union Street	Northern end of SR 117 concurrency
		29.75	47.88	SR 81 east (North Street) / Union Street	Southern end of SR 81 concurrency
		29.94	48.18	SR 81 west / SR 309 west (North Street) / Elizabeth Street	Northern end of SR 81 / SR 309 concurrencies
	American–Bath township line	33.81	54.41	SR 115 north – Kalida	Southern terminus of SR 115
	Monroe Township	35.73– 35.95	57.50– 57.86	US 30 – Beaverdam, Delphos	Interchange
Putnam	Columbus Grove	42.45	68.32	SR 12 (Delphos Road)
	Ottawa	49.70	79.98	US 224 / SR 15 east (Main Street) / SR 109 begins	Southern end of SR 15 / SR 109 concurencies
		50.17	80.74	SR 15 west (Defiance Street) / Taft Avenue	Northern end of SR 15 concurrency
		50.45	81.19	SR 109 north (Locust Street)	Northern end of SR 109 concurrency
	Leipsic	57.52	92.57	SR 613 (Main Street)
Henry	Bartlow Township	67.64	108.86	SR 18 east – Deshler	Southern end of SR 18 concurrency
		68.52	110.27	SR 18 west / CR E – Hamler	Northern end of SR 18 concurrency
	Richfield Township	72.54	116.74	SR 281 – Defiance, Custar
	McClure	78.59	126.48	US 6 (North Street)
	Damascus Township	81.61	131.34	SR 110 west – Napoleon	Eastern terminus of SR 110
Wood	Grand Rapids	85.96	138.34	SR 295 north / Bridge Street	Southern terminus of SR 295
	Washington Township	90.60	145.81	SR 235 south (Otsego Pike) – Weston, Hoytville, McComb	Northern terminus of SR 235
	Middleton Township	93.28	150.12	SR 582 east	Western terminus of SR 582
		96.14	154.72	SR 64 south	Southern end of SR 64 concurrency
		96.70	155.62	SR 64 north – Waterville, Whitehouse	Northern end of SR 64 concurrency
	Perrysburg	102.43	164.85	SR 25 south (West Boundary Street) / Indiana Avenue	Southern end of SR 25 concurrency
		102.69	165.26	US 20 west / SR 25 north / Front Street	Northern end of SR 25 concurrency; southern end of US 20 concurrency
		103.36	166.34	US 20 east (Louisiana Avenue)	Northern end of US 20 concurrency
Lucas	Toledo	109.54– 109.72	176.29– 176.58	I-75 – Dayton, Detroit	Exit 199 (I-75)
		111.61	179.62	SR 2 east / SR 51 south (Woodville Road) / Oak Street	Southern end of SR 2 / SR 51 concurrencies
	Maumee River			Anthony Wayne Bridge
	Toledo	112.41	180.91	SR 2 west (Summit Street) / Clayton Street	Northern end of SR 2 concurrency
		112.90	181.69	SR 51 north (Monroe Street)	Northern end of SR 51 concurrency
		113.45	182.58	SR 120 west (Cherry Street)	Eastern terminus of SR 120
	Maumee River			Robert Craig Memorial Bridge
	Toledo	115.01– 115.84	185.09– 186.43	I-280 / LECT / Front Street – Cleveland, Detroit	Exit 9 (I-280)
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus