First called Corpus Christi Island or Isla Santiago, Padre Island was named for Padre Jose Nicolas Balli (177?-1829). His family migrated from Spain in 1569 and became large landowners in the lower Rio Grande Valley, influential in military and governmental affairs. Ordained about 1790, Padre Balli applied to Spain's King Charles IV in 1800 for 111/2 leagues of land on the island.

Padre Balli had the land surveyed and in 1804 started the first settlement, Rancho Santa Cruz, about 26 miles from the southern tip. He began the island's first mission for the settlers and to Christianize the Karankawa indians. With help from a nephew, Juan Jose Balli, as "Mayordomo" or Foreman, Padre Balli started ranching, bringing in large herds of cattle, horses, and sheep. Padre Balli served as missionary and the collector of finances for all churches in the Rio Grande Valley. With financial aid from his mother Dona Rosa Maria de Hinojosa, he opened the first mission in present Cameron County and began a church and the first school at present Matamoros, Mexico. Padre Balli's ministry influenced the lives of early settlers in south Texas. He was buried near Matamoros.