Rodriguez was born in Bryan, Texas, the son of Diane and Roy Rodriguez, who own a tire shop called Rodriguez Tire. His siblings are brothers Ray and Roy Jr., and sister Raini Rodriguez, who is an actress. He is of Mexican descent.
Rodriguez had not considered becoming an actor until around 2006, when his sister began acting, stating in 2010 that he thought he would be "a NASCAR chef going to the moon".
In September 2009, he began playing Manny Delgado in Modern Family. He is a co-winner of the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series on two occasions (2011 and 2012), alongside the rest of the show's cast, and a nomination for the same award was garnered in 2010.