For decades, the depot served seven rail lines: the Duluth & Iron Range, the Duluth Missabe & Northern, the Duluth Superior & Western, the Great Northern, the Northern Pacific, the St. Paul & Duluth, and the Duluth South Shore & Atlantic. It also housed the depot's offices, a newsstand, a barber shop, a parcel room, and a lunch room. Due to decreased demand for passenger rail service throughout the country, ridership declined at the depot and the last train left in 1969 with ten people on it, all of whom wanted to be among the last few to ride a train from the station.
Fearing that the depot would be demolished, Duluth citizens came to its rescue. As a result of their efforts, the depot was saved and named to the National Register of Historic Places in 1971. It is after this point that passenger service returned to the depot. Amtrak offered rail service to and from St. Paul beginning in 1974. This was popular but after ten years it ended—the last train departed on Easter Sunday 1985—due to lack of funding.
Along with the Amtrak service, the depot saw a rebirth in other ways during the 1970s. A group of four prominent Duluth citizens came together and started a campaign to renovate the station and transform it into a center for arts, culture, and history. The Duluth Junior League raised $250,000 and the rest of the money, which amounted to $4.5 million dollars, came in the form of grants. The construction of a new train museum was included in the plans. The entire project, which began in 1973, went over budget but it was completed by the late 1970s.
The depot continues to be a place to for arts, culture, and history. However, a new rail line, the Northern Lights High Speed Rail, may return passenger service—and high speed rail—to the depot in the coming years. Minnesota received a federal grant to undertake a preliminary environment and engineering review of the project.