Melchor Casco de Mendoza (1581–1658) was a Spanish nobleman, alcalde and alferez real of Buenos Aires.

[1] He also served as regidor of Asuncion in 1620.

[2] Melchor was born in Asuncion, the son of Víctor Casco de Mendoza and Lucía Valderrama, daughter of Juan de Fustes.

[3] He was married to Catalina Astor, daughter of Pedro de Izarra Astor and Úrsula Gómez y Luyz.

[4] Melchor Casco de Mendoza was grandson of Gonzalo Casco and María Mendoza, daughter of Gonzalo de Mendoza and Isabel Irala (daughter of Domingo Martínez de Irala).