The highway runs through the southern incorporated limits of the city of Fort Myers and through the mid part of Cape Coral, and has become a major commuter route.

After crossing the Caloosahatchee River on the Midpoint Bridge into Fort Myers the highway, it is known as Colonial Boulevard, a controlled-access road.

The route intersects State Road 739 (Metro Parkway) and passes by the Calusa Nature Center and Planetarium before interchanging with Interstate 75 west of Lehigh Acres.

[5] The opening of the Edison Mall in 1965 at the corner of US 41 brought additional traffic to Colonial Boulevard, which was widened to four lanes in the early 1970s.

[15] Veterans Parkway initially ran as far as Santa Barbara Boulevard, but it was extended to Pine Island Road (SR 78) by 2002.

[16] In the late 2000s, improvements were planned for the corridor between Chiquita Boulevard in Cape Coral and I-75, which included additional overpasses and express lanes.