Named after Joseph Nicollet, the hotel quickly became a landmark and many of the city's early prominent figures such as John S. Pillsbury and William D. Washburn worked out of it.

[3] The building was designed by the Chicago-based firm of Holabird & Roche in a somewhat plain and unadorned style with four wings of rooms arranged around a central core.

One of the hotel's lounges, the Minnesota Terrace, hosted musicians such as Glenn Miller, Artie Shaw, Tommy Dorsey, Gene Krupa and Lawrence Welk.

During the 1960s when much of the Gateway District was demolished as part of an urban renewal project the Nicollet was spared, however the hotel's age and the neighborhood's decline left it unable to compete.

In 1973 the hotel was bought by Soul's Harbor Church which held services, operated Calvary Bible Institute, and provided housing in the building.