The station was listed on the National Register of Historic Places as the Chicago, Milwaukee and St. Paul Railway Depot and was renovated in 2001.

The 1858-built station was replaced by in 1878 by the Cameron House, a combined depot and hotel located near downtown La Crosse.

[2] The Milwaukee Road authorized a taxi company to carry passengers between downtown La Crosse and the station for a flat fee.

[6] Over the years, service gradually decreased as subsidies for automobile and air travel cut into the profitability of passenger rail.

By October 1970, only the daily Morning Hiawatha round trip plus the Minneapolis-to-Chicago Fast Mail served La Crosse.

Amtrak retained the Burlington Northern Railroad's Empire Builder, but rerouted it between Minneapolis and Chicago, replacing the Morning Hiawatha on a similar schedule.

The North Star was cut back to a Minneapolis–Duluth service in October 1981, leaving only the daily Empire Builder serving La Crosse.