Port Isabel is located in Cameron County in far south Texas in the Matamoros-Brownsville metropolitan area. Port Isabel is about 135 nautical miles (192 kilometers or 119 miles south) from the Port of Corpus Christi. Port Isabel is about 242 nautical miles (426 kilometers or 265 miles) south of the Port of Tampico in Mexico. Located on the Gulf Intracoastal Waterway, Port Isabel was home to just over five thousand people in 2010.

The Port Isabel was the last area in the Texas Gulf Coast to be settled by the Spanish because of its harsh environment. In the 1770s, there was a small fishing village called "El Fronton de Santa Isabel" in the location of today's Port Isabel.

From the 1770s until the 1840s, the future Port Isabel was popular with ranching families as a summer resort. In 1842, Mexico established a customs house for the Port of Matamoros at the modern site of the Port Isabel lighthouse.

In 1846, General Zachary Taylor established Fort Polk at the site of Port Isabel's Lighthouse Square, and he renamed the town "Point Isabel." During the Texas War for Independence, Port Isabel was transformed into a boom town. The California Gold Rush of the mid-1800s created a small boom in Port Isabel as fortune-hunters sought a safe route through Mexico to the gold fields. One of those travelers was James Audubon who recorded local plants and wildlife.

In 1852, the lighthouse was built at Point Isabel. Confederate troops used the lighthouse during the American Civil War to spy on Union soldiers. In 1864, there was a small battle at the Port Isabel docks near the lighthouse. The Confederates tried unsuccessfully to blow up the lighthouse. During the Civil War, the Brazos Santiago hospital treated more than 100 thousand patients, mostly victims of illnesses like yellow fever, cholera, and dysentery.

The last Civil War battle on land, the Battle of Palmito Hill, was fought about nine miles south of Port Isabel. Although the Confederates won the battle, they had to surrender to Union troops when the South lost the bigger war. In 1867, a powerful hurricane destroyed Port Isabel.

The Rio Grande Railroad from Port Isabel to Brownsville started operating in 1872, bringing a prosperous era to Port Isabel as people came to the popular summer resort and seaport.

In the latter decades of the 1800s, Port Isabel became a busy commercial fishing port. Huge amounts of fish were shipped from Port Isabel to Brownsville and Mexico. In 1898, Port Isabel was a departure point for steamers carrying American troops going to the Spanish American War.

In 1909, a channel with a depth of 3.7 meters (12 feet) was cut from Brazos to the Port Isabel docks. Due to "bandit activities," US troops from Illinois and Iowa were stationed at Port Isabel.

In the 1920s, Port Isabel grew in popularity as a sport fishing center, attracting more tourists. The first Texas International Fishing Tournament was held in Port Isabel in 1934.

Between 1943 and 1945, Port Isabel came under alert several times from German U-boats, and many enemy submarines were sunk in the Gulf of Mexico near Port Isabel.

In 1954, a new era of growth began when the first Queen Isabella Causeway was completed. A new Queen Isabella Causeway opened in 1984. In 2001, eight people died when a barge hit the causeway and caused a section to collapse. The causeway was then renamed to the Queen Isabella Memorial Bridge.

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