North of Kansas City, the highway travels north-northeast toward the Iowa state line near Eagleville, paralleling U.S. Route 69 (US 69).

I-35 enters Missouri two miles (3.2 km) southwest of Downtown Kansas City as a six-lane highway.

Along the loop's northern edge, I-35 runs concurrent with I-70 immediately west of Broadway Boulevard and carries six lanes of traffic with a speed limit of 45 mph (72 km/h).

[2][5] Jefferson Lines provides intercity bus service along the length of I-35 in Missouri serving three communities along the route.

is a business loop of I-35 in the town of Cameron, stretching just over three miles (4.8 km) between exits 52 and 54 on the westside of I-35.