De Vargas is a surname of Spanish origin. Notable people with the surname include:
Andrés de Vargas (1613–1647), Spanish painter Diego de Vargas (1643–1704), Spanish colonial governor Francisco de Vargas (born 1970), Paraguayan lawyer and politician Francisco de Vargas y Mejía (1500–1566), Spanish diplomat and writer Gutierre de Vargas Carvajal (1506–1559), Spanish Roman Catholic bishop José de Vargas Ponce (1760–1821), Spanish erudite, poet and writer Luis de Vargas (1502–1568), Spanish Renaissance painter Urbán de Vargas (1606–1656), Spanish Baroque composer Valentin de Vargas (1935–2013), American actor