Harlingen is located at the intersection of U.S. highways 77 and 83 in southwestern Cameron County.

In 1904 Lon C. Hill envisioned the Arroyo Colorado as a commercial waterway. Though the early days saw railroad workers calling the rugged stop between Corpus Christi and Brownsville "Rattlesnake Junction," Hill named this town on the north bank of the arroyo after a city in Holland because the irrigation canals were similar to that country's waterways. The first school opened with fifteen pupils in 1905 near the Hill home, which the first residence built in Harlingen. Harlingen was incorporated on April 15, 1910, when the population totaled 1,126. The local economy at first was almost entirely agricultural with the major crops being vegetables and cotton.

The town center was Van Buren and Hill (now First) Streets, where the railroad built a two-story hotel with two baths in 1906. Other early buildings near the tracks included two general stores, hardware and drug stores, a barbershop, four saloons, a blacksmith shop, and a Texas Rangers headquarters. Crowds of Rangers, customs officers, and residents gathered at pistol ranges near the depot, giving rise to yet another nickname, "Six Shooter Junction."

As time went on, the town became a city. Harlingen's strategic location in the Valley helped it grow into a thriving military center and a trade and transportation hub. World War II military installations in Harlingen caused a jump in population from 23,000 in 1950 to 41,000 by 1960. Harlingen Army Air Field preceded Harlingen Air Force Base, which closed in 1962. The city's population fell to 33,603 by 1972, then climbed to 40,824 by 1980. Local enterprise, focused on the purchase and utilization of the abandoned base and related housing, laid the groundwork for continuing progress through a diversified economy. The estimated population in July 1985 was 49,000, of which about 80 percent was Hispanic. In the late 1980s income from tourism ranked second only to citrus fruit production, with grain and cotton next in order. The addition of wholesale and retail trade, light and medium manufacturing, and an array of service industries has broadened the economic base. Large-scale construction for multifaceted retirement communities is a new phase of industrial development.

Each March Harlingen is the site of the Rio Grande Valley International Music Festival. Many remarkable old buildings that have been restored to new life as homes and offices, shops, banks, and cafes.