It runs east on Main Street from WIS 35 (Second Avenue) in downtown Onalaska to the US Highway 53 (US 53) freeway.

At this point, not only does the roadway become an expressway, US 53 briefly runs concurrently with WIS 157.

At the next interchange north, WIS 157 leaves the expressway to travel due west to downtown Onalaska.

[2] Initially, in 1923, WIS 157 briefly appeared to serve Briggsville via present-day County Trunk Highway AA (CTH-AA).

This new routing traveled mostly along CTH-M from WIS 32 in Frostville to US 141 in between Coleman and Lena.