The list of railroads that jointly operated Kansas City Union Station reads like a roll call of American transportation history: the Atchison, Topeka and Santa Fe; Chicago, Burlington and Quincy; Chicago, Rock Island and Pacific; Kansas City Southern; Missouri Pacific; Union Pacific; and six others. At its peak in 1945, at the close of World War II, the station handled more than 670,000 passengers annually. Soldiers shipping out and coming home passed through the Grand Hall beneath that massive clock face, their footsteps echoing across floors designed to move crowds efficiently from ticketing to the perpendicular waiting hall extending out above the tracks. The station was not merely a building; it was the physical expression of Kansas City's position as a central hub connecting the coasts.

On June 17, 1933, the station became the site of one of the most notorious crimes in American history. Federal agents and police officers were escorting captured fugitive Frank Nash through Union Station to a waiting car when gunmen opened fire with Thompson submachine guns. Four lawmen were killed, along with Nash himself, in an attempt by the Kansas City underworld to free the prisoner. The Kansas City Massacre, as it was immediately dubbed, exposed the lawlessness of Tom Pendergast's Kansas City and directly led Congress to grant FBI agents the authority to carry firearms and make arrests. The thirty-second gunfight outside the east entrance changed the nature of federal law enforcement permanently.

The same forces that killed passenger rail across America hollowed out Union Station. Traffic plummeted through the 1950s. The building deteriorated. By 1983, the station had largely closed, with Amtrak's operations confined to a small "bubble" inside the Grand Hall. Even that indignity ended in 1985, when all passenger operations were moved to a smaller facility adjacent to the old station. The city sued developer Trizec, which had built two office buildings on surrounding property but failed to redevelop the station, and settled in 1994. That settlement helped fund just under half of the ambitious plan that would save Union Station.

In 1996, a public-private partnership launched a $250 million restoration, funded in part by a bistate sales tax levied across Kansas and Missouri counties. By 1999, Union Station had reopened not merely as a train station but as a cultural destination. Science City brought more than 50 hands-on exhibits. The Regnier Extreme Screen, five and a half stories tall, became the region's largest movie venue. Restaurants, shops, a planetarium, and rotating museum exhibitions filled the grand spaces. Train service returned in 2002 when Amtrak resumed operations, making Kansas City Missouri's second-busiest train station. The KC Streetcar began stopping at Union Station in 2016, connecting it to the River Market and downtown. The 2023 NFL Draft was held in front of and partially inside the station, and four Amtrak trains serve it daily, including the Southwest Chief running between Chicago and Los Angeles. The Grand Hall chandeliers, all 3,500 pounds of each, still hang overhead.