There was a claim made at the time that it was the largest railroad station in the Southern United States, covering forty acres (16 ha).

[5] Union Station provided the entrance to Louisville for many visitors, with its height being the 1920s, when it served 58 trains a day.

Many of those traveling to the Kentucky Derby would use the Union Station as their first place of celebration, with twenty special trains coming to the facility, and Pullman cars allowing overnight accommodations, a trend that continued until the mid-1960s.

The rose-colored windows were replaced due to the fire with an 84-paneled stained glass skylight that became a feature of the barrel-vaulting tower.

[5] Amtrak used the facility regularly from May 1971 until October 1976, when it began running the Floridian in conjunction with the Auto-Train from a suburban station near Louisville International Airport.

From December 4, 2001, to July 4, 2003, a track on the west side of the parking lot served Amtrak's Kentucky Cardinal, which ran to Chicago via Indianapolis.

This was primarily because the Indianapolis-Louisville leg ran along jointed rail that limited its speed to 30 miles per hour (48 km/h), slower than automobile traffic along Interstate 65.

[5] In October 2010, TARC announced plans to use a grant from the U.S. Department of Transportation to restore all 278 windows at the 120-year-old Union Station, including 40 made of stained glass.