The station opened on August 3, 1965, as Milwaukee Union Station. Operated by the Milwaukee Road, it replaced their previous Everett Street Depot. The depot was built on West St. Paul Avenue in a modernistic style that proved unpopular quickly after it was erected.[3] The Chicago and North Western Railway closed their Milwaukee station (Lake Front Depot) and moved their passenger operations to the new Milwaukee Road depot in 1966. Following the formation of Amtrak in 1971, the Chicago and North Western withdrew all of its inter-city trains and commuter service from the station. The Canadian Pacific Railway (through its Soo Line Railroad subsidiary) acquired the trackage within the train shed when it bought the remnants of the Milwaukee Road in 1986. CP merged with the Kansas City Southern Railway on April 14, 2023 to form Canadian Pacific Kansas City Limited.
In November 2007, the facility was renamed the Milwaukee Intermodal Station following a $16.9 million renovation. The new facility included a larger waiting area with a glass atrium and improved space for Amtrak ticketing, as well as facilities for intercity buses (to accommodate Greyhound service after it relocated from its former location at 7th and Michigan), a restaurant, and retail space.[4] In 2016, the Wisconsin Department of Transportation completed a rebuild of the train shed and platform to meet federal accessible standards.[5]
The Hop streetcar service began on November 2, 2018, with a stop on Vel R. Phillips Avenue just northeast of the station.