IU Northwest is the result of growth and change that began in 1921 when the university offered its first formal classes in Lake County as part of a program sponsored by the Gary Public School System. Under various names and in various locations, Indiana University has been serving the needs of higher education in northwest Indiana ever since.

In 1932 Indiana University initiated the Calumet Center in East Chicago; and by 1939, through funds granted by the state legislature and the federal government, the Calumet Center was serving students in a building in Tod Park on a site donated by the City of East Chicago.

When Gary College was founded in 1933, Indiana University discontinued classes in Gary except for a few advanced courses. But in 1948, at the request of the Gary School Board, the university assumed the management of Gary College, which became the Gary Center of Indiana University. Gary Center classes were held after school hours and in the evenings at the Horace Mann High School until 1949, when all the main facilities of the center were moved to the commercial wing of the City Methodist Church, a move that allowed for a considerable expansion of the center's program. In 1955, with approval from the Gary Board of Park Commissioners, the Common Council of the city authorized the sale of 27 acres of Gleason Park to Indiana University for the purpose of establishing a Gary Center campus (the present site of IU Northwest). In May of 1959, the first classes were held in the new location.

Recognizing the growth of such centers and the increasing demands for higher education throughout the state, Indiana University in 1963 reorganized its various "extension" centers into regional campuses, and the Gary Center and the Calumet Center became the Northwest Campus of Indiana University. Soon after this reorganization, the first degree programs were authorized, and the Northwest Campus became a four-year college. The first commencement was held at the Northwest Campus in June of 1967. In 1968, the IU Board of Trustees changed the name of the Northwest Campus to IU Northwest.