Marquette was born in Dallas, Texas to parents Patricia Helen "Tisha" (née Marquette) and Jorge Luis "George" Rodriguez, a nuclear engineer. He has two older brothers, Eric and Chris, who are both active in entertainment. His father is of Cuban descent.
Marquette made his acting debut in 1995 when he landed the role of Jamie Martin on the ABC soap opera series All My Children. He has since gone on to star in other productions including 13 Going on 30 (2004), Ultimate Spider-Man (2005), and Van Wilder: Party Liaison (2002). He is perhaps best known for his roles as Mac on Cartoon Network's Foster's Home for Imaginary Friends (2004-2009), and Johnny Atkins on the ABC sitcom The Goldbergs (2013-present) and its spin-off series Schooled (2019-2020).