This area, originally known as Highlands or Highlands Bayou, was part of a Republic of Texas land grant awarded to John Moore in 1838. The early economy developed as agricultural, with an emphasis on dairy farming. In 1853, the Galveston, Houston & Henderson Railroad was chartered and tracks were laid between Houston and Galveston, with La Marque in its path. Eventually, the town would also be a stop for the Interurban on the Galveston and Houston Electric Railway. For a time, the stop was known as Buttermilk Station, presumably because Civil War soldiers would stop there and drink buttermilk.

In 1886, the U.S. postal service requested that a new name be selected for the town because mail delivery was being confused with the town of Highland in Erath County. Tradition states that Madame St. Ambrose, the local schoolmistress and French nun, chose the name La Marque, which is French for “the mark.”

A notable part of La Marque’s history is the area now listed on the National Register of Historic Places as the Settlement Historic District. The site of the oldest Creole Cottage style home remaining in the county, as well as other structures, was a community of black cowboys. These men contributed to the success of area cattle industry, including the Butler Ranch, with their specialized skills like cattle driving and bronc busting.