Republic Airlines came to being in 1979 with the merger of North Central Airlines and Southern Airways. The new airline's headquarters was at Minneapolis-Saint Paul International Airport though its largest and main hub was at Detroit Metropolitan Wayne County Airport. At the time of its formation, Republic was the sixth largest airline in the United States. In 1980, following its buyout of Hughes Airwest, Republic became the largest airline in the United States by destinations served. The route network was served with the world's largest Douglas DC-9 fleet and also Boeing 727s.

On January 23, 1986, Northwest Orient Airlines announced that it would purchase Republic for $884 million in response to United Airlines' purchase of the Pacific routes of Pan American World Airways and in order to provide the domestic feed it required to compete effectively. The merger was completed on October 1, 1986 with Northwest dropping the word Orient from its brand name after the merger. Republic operated hubs at Minneapolis-Saint Paul International Airport, Memphis International Airport, and Detroit Metropolitan Wayne County Airport. These airports are now the backbone of Northwest's domestic route network.

Despite Northwest's ongoing efforts to remove all remaining presence of any Republic-branded imagery, as of 2007, it is still possible to find a few old Republic logos around Minneapolis-Saint Paul International Airport and Memphis International Airport. The logos can no longer be seen at Detroit Metropolitan Wayne County Airport because Northwest's old terminal has been demolished. Northwest was subsequently purchased by Delta Air Lines, with Delta to be the surviving brand.