Tifton was founded in 1872 by sawmill owner Henry H. Tift. The city was located at the junction of the Georgia Southern and Florida Railroad and the Brunswick and Western Railroad in Georgia. The Tifton Residential Historic District is part of the National Register of Historic Places.

At the time, Tifton was known as the "Gate Town" and served as a gateway to the south. Several Chicago-Florida passenger trains stopped at Tifton, and it has been and remains an important part of the region's growth.

Tifton's dominance in the region was established after the incorporation of the city in 1890. Tifton's early notoriety also stems from its location on the Georgia-South Carolina border and its proximity to the Mississippi. Other highways that run through the city are the US-Georgia Line, I-285, and Interstate 5. The construction of the Atlanta-Atlanta Expressway in the late 1890s and the opening of a new Atlanta-Atlanta rail line in 1896 cemented Tifton's place as a transportation center.

Tifton's sagacious beginnings led to two institutions that still exist today: the University of Georgia Tifton Agriculture Campus and the Abraham Baldwin Agricultural College. Both institutions attract large numbers of farmers, scientists, and educators, with the state employing plant pathologists at experimental stations and helping develop the first covered open-air garden in the United States.

The city is also home to the Tifton Campus of the Southern Regional Technical College.

The world's second-largest magnolia tree is located in Magnolia Tree Park, and Tifton recently hosted the opening of a new museum, the Tift County Museum of Natural History. Tifton is conveniently located off Interstate 75, which runs north to south for about 100 miles to Atlanta. North of the city is a public airport, Tifting County Airport, which serves general aviation with scheduled commercial airlines.

The fertility of the land attracted people from all over the country, and even in the 19th century, Tifton owned an opera house built in the 1890s.

The racial makeup of the city is a mix of African-Americans, whites, blacks, Hispanics, Asians, and Native Americans. The median household income in Tifton was $35,927 in 2015.