Denver's railroad story began in 1868 with a modest station serving the Denver Pacific Railway. By 1875, four competing lines had built separate depots across the city, forcing passengers to shuttle between stations when changing trains. The solution came in 1880 when the Union Pacific, Denver & Rio Grande, Denver South Park & Pacific, and Colorado Central railroads agreed to build a single "Union Station" at 17th and Wynkoop. That first station opened in May 1881, complete with a central clock tower. Thirteen years later, a fire that started in the women's restroom gutted the central portion. The Kansas City architectural firm Van Brunt & Howe designed a Romanesque Revival replacement, but by 1912, passenger traffic had outgrown even this structure. Denver architects Gove & Walsh demolished the center section once more, creating the current Beaux-Arts edifice that opened in 1914.

On July 4, 1906, a ceremonial arch rose before the station's entrance, offering travelers a symbolic gateway to the city. The Mizpah Arch welcomed dignitaries throughout the 1920s and 1930s, when over eighty trains served the station daily. Queen Marie of Romania passed beneath it, as did Presidents Theodore Roosevelt, William Howard Taft, and Franklin Delano Roosevelt. But the automobile age was coming. By 1931, the beloved arch had become a traffic hazard and was torn down. Passenger service declined through mid-century until Amtrak became the sole rail provider, running just two daily California Zephyr trains between Chicago and the Bay Area.

The station's second life began in 2001 when the Regional Transit District bought the property and its surrounding nineteen acres. A 2004 tax measure provided funding, and a $300 million federal grant in 2010 enabled construction of a modern transit complex. The historic building closed in December 2012 and reopened in July 2014 as something new: the 112-room Crawford Hotel occupies the upper floors, while the ground-level Great Hall serves simultaneously as hotel lobby, Amtrak waiting room, and public gathering space. The original chandeliers have returned, though the old wooden benches with their built-in heating and lighting were removed due to asbestos concerns. Ten independent restaurants and retailers now fill the ground floor.

Behind the historic facade, a thoroughly modern transit network has taken shape. An open-air train hall serves Amtrak and commuter rail lines. Below street level, a 22-gate bus concourse stretches two city blocks westward, handling RTD buses, Bustang state routes, Greyhound, and Burlington Trailways. The A Line commuter rail launched in April 2016, connecting downtown to Denver International Airport in thirty-seven minutes. Additional lines now reach Westminster, Wheat Ridge, and Thornton. The station that once linked Denver to the transcontinental railroad now anchors a regional transit network serving over 100,000 passengers daily, all while maintaining its role as the social heart of the LoDo district.