Illinois Route 251 is a north–south state highway that runs on the former alignment of U.S. Route 51 before Interstate 39 was built in north central Illinois. It runs from U.S. 51 at the border with Wisconsin to I-39 and U.S. 51 south of Kappa. Illinois 251 is 135.32 miles (217.78 km) long.

Illinois 251 runs parallel to Interstate 39 and U.S. 51 for most of the length of I-39 in Illinois. Like Illinois Route 351, it can be considered a spur, loop or alternate of its parent route, U.S. 51. Illinois 251 terminates about 8 mi (13 km) north of the southern terminus of I-39.

The road parallels the east bank of the Rock River through Rockford, where the highway goes north on Eleventh Street, west on Harrison, north on Kishwaukee, west on Walnut then split between northbound Third and southbound Second through downtown Rockford. After downtown, both directions take the southbound lanes' Second Street name as a divided urban expressway (also badged as Martin Luther King Jr. Memorial Drive) for a couple of miles north of downtown Rockford. It stays Second Street through Loves Park, Machesney Park and Roscoe until its north endpoint at US 51 and Illinois 75 in South Beloit, .25 miles (0.40 km) short of the Wisconsin state line.

Illinois 251 was established in 1982 when first segment of I-39 opened between Rockford and Bloomington. In 1992, the final segment of I-39 opened north of Bloomington. The remaining stretch of former U.S. 51 became Illinois 251. The initial designation of I-39 was U.S. Route 51 until 1992.

County	Location	mi	km	Destinations	Notes
McLean	​	0.0	0.0	I-39 / US 51 – Bloomington–Normal, Rockford	Southern terminus; I-39 exit 8
Woodford	El Paso	7.1	11.4	US 24 (West Main Street)
	​	15.2	24.5	IL 116 west	South end of IL 116 overlap
	​	16.2	26.1	IL 116 east	North end of IL 116 overlap
Marshall	​	27.6	44.4	IL 17 west	South end of IL 17 overlap
	Wenona	29.6	47.6	IL 17 east (Elm Street)	North end of IL 17 overlap
LaSalle	​	34.6	55.7	IL 18 (North 13th Road)
	Tonica	41.7	67.1	CR 54 (Ray Richardson Road, Ed Lambert Road)
	​	44.8	72.1	IL 71 / IL 351 north
	​	45.6	73.4	I-39 / US 51 – Bloomington–Normal, Rockford	I-39 exit 52
	Illinois River	49.6	79.8	Peru Bridge
	Peru	49.8	80.1	US 6 – LaSalle, Spring Valley	Interchange
	​	52.5	84.5	I-80 – Moline, Rock Island, Joliet	I-80 exit 75
	​	55.7	89.6	CR 33 (North 33rd Road)
	​	59.7	96.1	US 52 east (North 37th Road)	South end of US 52 overlap
	Mendota	65.1	104.8	US 34 (Washington Street, Walter Payton Memorial Highway)
		66.1	106.4	US 52 west	North end of US 52 overlap
Lee	​	81.6	131.3	US 30
Ogle	​	91.7	147.6	I-88 Toll / IL 110 (CKC) (Ronald Reagan Memorial Tollway) – Chicago, Moline, Rock Island	I-88 exit 76
	Rochelle	93.1	149.8	IL 38 west / Lincoln Highway (Lincoln Avenue)	South end of IL 38 overlap
		94.0	151.3	IL 38 east / Lincoln Highway (May Mart Drive)	North end of IL 38 overlap
	Hillcrest	99.0	159.3	IL 64
	Davis Junction	105.8	170.3	IL 72 (Chicago Avenue)
Winnebago	Rockford	114.0	183.5	US 20 (Rockford Bypass, Ulysses S. Grant Memorial Highway) – Freeport, Belvidere	Interchange
		118.1	190.1	US 20 Bus. (1st Avenue, Jefferson Street)
		118.7	191.0	Whitman Street Bridge	Interchange
		120.1	193.3	Auburn Street, Spring Creek Road	Interchange
		120.6	194.1	Forest Hills Road	Northbound exit and southbound entrance
	Machesney Park	125.7	202.3	IL 173 east (West Lane Road)
	Roscoe	132.8	213.7	CR 76 (Prairie Hill Road)
	Rockton	133.8	215.3	CR 9 (Rockton Road)	Interchange
	South Beloit	135.32	217.78	US 51 / IL 75 (Gardner Street)	Northern terminus
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus       Incomplete access

• Illinois Highway Ends: Illinois Route 251