He was treasurer to the Spanish expedition under Pánfilo de Narváez that reached what is now Tampa Bay, Florida, in 1528.
Cabeza de Vaca deplored the Spanish explorers' treatment of Indians, and when he returned home in 1537 he advocated for changes in Spain's policy. After a brief term as governor of a province in Mexico, he became a judge in Seville, Spain, a position he occupied for the remainder of his life.