Santa Maria is a census-designated place in Cameron County, Texas, United States. The population was 651 at the 2020 census. It is part of the Brownsville–Harlingen Metropolitan Statistical Area. Santa Maria is located near the southwestern corner of Cameron County at 26°4′41″N 97°50′53″W / 26.07806°N 97.84806°W. U.S. Route 281 passes throu…Santa Maria is a census-designated place in Cameron County, Texas, United States. The population was 651 at the 2020 census. It is part of the Brownsville–Harlingen Metropolitan Statistical Area. Santa Maria is located near the southwestern corner of Cameron County at 26°4′41″N 97°50′53″W / 26.07806°N 97.84806°W. U.S. Route 281 passes through the CDP, leading southeastward 27 miles to Brownsville and west 26 miles to Hidalgo. The community is approximately one mile north of the Rio Grande, which forms the Mexico–United States border.