The area was first settled by ranchers as early as 1770. The town was originally called El Fronton or El Fronton de Santa Isabel and was located about three miles from the present Port Isabel lighthouse. In 1820, the ranchers, led by Fray Nicolas Balli, took their herds across Laguna Madre to Padre Island to preserve them from raiding parties during the Mexican War of Independence. In 1846, Zachary Taylor used the point for a base for supplies and called it Fork Polk, honoring President Polk. Later, it became a port of entry for westbound California gold-seekers.

It was during the Mexican war that El Fronton came to be called Point Isabel, for the historic Spanish land grant of Santa Isabel and for it's location on a point across from Brazos Santiago in southeastern Cameron County. In the 1930's the name was then changed to Port Isabel, as deep water dredging made the port an important shipping center.

The brick lighthouse, built in 1853, was abandoned in 1906. Now a state park, it stands as a monument to the early men and ships that came in to the port seeking safety from storms or buccaneers, as well as merchants seeking trade and daring adventurers.

Today Port Isabel is a popular summer resort for people of all ages and harbors great sea food restaurants.