It runs from Interstate 41 (I-41) in the Town of Grand Chute east to WIS 47 in Appleton; the route is located entirely within these two municipalities.

WIS 125 begins at a junction with I-41 and County Trunk Highway CA (CTF-CA) in the Town of Grand Chute.

From here, the route heads east as a divided highway called College Avenue, passing through a business district.

The highway runs through a mixed residential and business area, passing to the south of Wilson Middle School.

[2][3] Valley Transit's Route 15 West College bus serves much of WIS 125, including the entire eastern half of the road.