I-44 enters Missouri in Newton County at the eastern terminus of the Will Rogers Turnpike, 200 yards (180 m) south of the Kansas state line.

This highway next goes through southern Joplin and then begins to run concurrently with I-49/US 71 at exit 11 just after entering Jasper County.

At Halltown, the road curves back to due east, beginning to follow the general pathway of old US 66, which it does all the way to downtown St. Louis.

I-44 then bisects Eureka before serving as the southern boundary of Route 66 State Park (the former site of Times Beach, known for its dioxin contamination and its eventual demolition and Superfund cleanup[citation needed]).

I-44 then goes through Crestwood, Kirkwood, Oakland, Webster Groves, and Shrewsbury before entering the city of St. Louis.

The two highways run concurrently for about two miles (3.2 km) until I-55 turns east at an interchange with I-64 to cross the Mississippi River on the Poplar Street Bridge.

This was changed when the Stan Musial Veterans Memorial Bridge opened on February 9, 2014, rerouting I-70 over the river along a more northern alignment.