In the U.S. state of Illinois, U.S. Route 24 is a major arterial road that runs from the Missouri state line at the Mississippi River in Quincy to Sheldon. This is a distance of 255.13 miles (410.59 km).

In Illinois, U.S. Route 24 may be divided into the following segments:

From Quincy to Peoria, the U.S. 24 route follows the old Peoria to Quincy stage coach route.

The U.S. 24 crossing into Illinois from Missouri over the Mississippi River consists of two bridges; westbound traffic uses the newer Bayview Bridge, while eastbound traffic uses the Quincy Memorial Bridge. At the eastern end of the Quincy Memorial Bridge, eastbound U.S. 24 overlaps Illinois Route 57 northbound (4th Street) for two blocks before Illinois 57 ends at Illinois Route 104 (Broadway); westbound U.S. 24 turns off onto the bridge at the northern terminus of Illinois 57. U.S. 24 continues north at Illinois 104 and serves only the northwestern portion of Quincy.

U.S. 24 overlaps Illinois Route 96 briefly before running due east. It has a full interchange with the northern terminus of Interstate 172; as of 2006, Illinois Route 336 continues northbound of I-172.

U.S. 24 then proceeds through a series of small towns; east of Camp Point, it intersects the southern terminus of Illinois Route 94. In Mount Sterling it briefly overlaps Illinois Route 99; Illinois Route 107 ends just south of U.S. 24. At this point, the highway turns northeast once again.

Just outside of Ripley U.S. 24 intersects the western terminus of Illinois Route 103. U.S. 24 then intersects U.S. Route 67 outside of Rushville. It enters Rushville from the west and exits north, on Kinderhook Road.

John Jacob Astor was the original owner of the tract upon which Astoria was platted in 1836 and served as an important way station on the original stage coach route.

U.S. 24 continues northeast and follows a series of concurrencies. West of Havana, U.S. 24 joins Illinois Route 100 northbound, and U.S. Route 136 westbound, forming a wrong-way concurrency. U.S. 136 leaves U.S. 24 and travels west at Duncan Mills, while U.S. 24 and Illinois 100 continue north to Lewistown. In Lewistown, the U.S. 24/Illinois 100 combination intersects Illinois Route 97 (Avenue E). Illinois Routes 97/100 run north while U.S. 24 eastbound joins with Illinois 97 southbound. U.S. 24/Illinois 97 meet Illinois Route 78, where Illinois 78/97 runs southbound and U.S. 24 eastbound joins with Illinois 78 northbound. The series of concurrencies ends in Little America, where Illinois 78 turns north and U.S. 24 continues northeast.

Illinois Route 9 overlaps U.S. 24 from Banner, through Kingston Mines and Mapleton, to where Illinois 9 splits and crosses the river to Pekin, Illinois.

North of the Pekin turnoff, U.S. 24 enters Bartonville as South Adams Street. Where Adams Street climbs a hill, U.S. 24 splits off onto McKinley Avenue, rejoining Adams Street just south of the Interstate 474 interchange.

U.S. Route 24 enters the South Side of Peoria at the Interstate 474 interchange. Streets parallel to the Illinois River are numbered southwest and northeast in Peoria, and U.S. 24 follows SW Adams Street to the beginning of SW Washington Street, then follows Washington Street for nearly Washington Street's entire length.

At the northwestern foot of the Cedar Street Bridge, U.S. 24 intersects a three-route concurrency of Illinois Routes 8, 29 and 116. Illinois 8/116 crosses Washington Street, continuing north towards Bradley University as MacArthur Highway. Illinois 29 northbound, however, joins U.S. 24 through the remainder of Peoria. At the foot of the Bob Michel Bridge, U.S. 24/Illinois 29 intersects Illinois Route 40, reaching the center of downtown Peoria.

Just after crossing Main Street, the routing of U.S. 24 and Illinois 29 becomes more complex for 4 blocks: NE Washington Street, NE Adams Street, and NE Jefferson Street are intersected by Hamilton Boulevard and Fayette Street and partially by Interstate 74 and Spalding Avenue. From southwest to northeast:

After this group of intersections, U.S. 24/Illinois 29 continues north on one-way NE Adams Street, with opposing U.S. 24/Illinois 29 traffic on one-way NE Jefferson Street. At the Averyville neighborhood, Jefferson Street splits from Adams Street; north of this, NE Adams Street is a two-way street carrying U.S. 24/Illinois 29 to the interchange with the McClugage Bridge.

At the McClugage Bridge, Illinois Route 29 and NE Adams Street becomes N. Galena Road and continues north past the bridge; U.S. 24 follows U.S. 150 across the bridge over the Illinois River.

On the other side of the bridge, eastbound U.S. 150 exits onto westbound Illinois Route 116 to form a wrong-way concurrency, but U.S. 24 continues past Illinois Central College east to Washington area on a four-lane divided highway. The highway continues to the interchange of Business U.S. 24 and the eastern terminus of Illinois 8, (Business U.S. 24 and Illinois 8 form an unsigned wrong-way concurrency at this point). Business U.S. 24 continues to Washington's town square on a four-lane undivided surface road, which eventually narrows to a two-lane road; the U.S. 24 bypass remains 4 lanes divided to Main Street north of Washington. The eastern terminus of Business U.S. 24 is between Washington and Eureka.

In Eureka, U.S. 24 has a stoplight with Illinois Route 117; there are also numerous signs to Eureka College and the Ronald Reagan Trail, as Eureka had prominence in President Ronald Reagan's early life. U.S. 24 then continues east, bypassing Secor to the south before interchanging with Interstate 39.

Just east of I-39, U.S. 24 serves as the main east–west road through El Paso, which largely serves as a stop for travelers on I-39. U.S. 24 travels through one other community, Gridley before having an interchange with Interstate 55 west of Chenoa.

East of Interstate 55, U.S. 24 has an intersection with former U.S. Route 66. It then passes through the towns of Fairbury, Forrest and Chatsworth, intersecting Illinois Route 47 in Forrest. Just south of Gilman, U.S. 24 has an interchange with Interstate 57 before overlapping U.S. Route 45 through Gilman. The two highways separate east of Gilman.

In Crescent City U.S. 24 intersects Illinois Route 49. In Watseka, it overlaps Illinois Route 1 through the town; the final concurrency, with U.S. Route 52 in Sheldon carries into Indiana.

The routing of U.S. Route 24 in Illinois is largely unchanged from 1926. Prior to 1937, U.S. 24 ran through Canton on various roads; afterwards it was relocated southeast, closely paralleling the Illinois River.

In 1995 a bypass around Washington was completed. The old U.S. 24 became an extension of Illinois 8 to between Washington and Eureka. In 1997, it was changed to Business U.S. Route 24, and Illinois 8 was truncated back to west of Washington.

Since the 1950s, U.S. Route 24 through Illinois and Missouri has been considered as one route of various Chicago to Kansas City federal interstate proposals (1956, 1968, 1972). None of these proposals received federal funding or support.