Although chosen as an ideal site for a port and a railroad terminus in 1887, it was 1902 before the Gulf & Ship Island Railroad's New York owner fulfilled the plan. As a planned city, Gulfport has broad streets laid out in a regular rectangular pattern paralleling the seawall. This was in marked contrast to the narrow-streeted antebellum towns along the rest of the coast. When completed, the railroad, which ran through sparsely settled sections rich in timber, transformed southern Mississippi.

Gulfport turned to the resort business in the 1920s and had a real estate boom in 1925 when the Illinois Central Railroad bought the Gulf & Ship Island line. The boom collapsed a year later after having produced Gulfport's tower apartments and many hotels. After World War II, luxury motels took over. With the Mississippi Sound and a great number of lakes, rivers, bays, and bayous within a few minutes drive from downtown, and with excellent facilities for deep-sea fishing, Gulfport is an angler's paradise.

Mississippi City, which has been incorporated into Gulfport, was the scene of the bare-knuckles fight for the heavyweight championship of the world on February 7, 1882, when John L. Sullivan beat Paddy Ryan under the live oaks now at the corner of Highway 90 and Texas Street.