Mario Hernandez was raised in Oxnard, California, the eldest of four brothers and one sister. Their mother had been an avid comic book fan as a girl, and entertained her children with drawings of her favorite characters. Mario was the first to discover comic books, and passed them along to his younger siblings. Comic books proliferated in the Hernandez household, with each child in turn developing an interest in drawing.
Mario Hernandez initiated the first issue of Love & Rockets in 1982 with brothers Gilbert and Jaime, and continued to contribute stories to many of the first issues. Mario's solo comic, Brain Capers, was published by Fantagraphics Books in 1993, featuring the best of his non-L&R work. He has also contributed to such anthologies as Angela Bocage's Real Girl.