Rodriguez was born in Zacatecas, Mexico. He became a permanent, nightly cast-member on Jimmy Kimmel Live! after performing in comedy segments written for the show. His broken English coupled with his affability and Teddy Bear-like quality have earned him a high-profile supporting role as a personality on the show. Guillermo took over main red-carpet interviewing duties in 2011 from the late "Uncle Frank" Potenza, whom he was often paired with for the show's comedic skits. Rodriguez's signature segment is "Guillermo's Hollywood Roundup", in which, dressed in a cowboy outfit and pretending to twirl a special effect operated lasso, he makes a mockery of entertainment news shows featured widely on television. From outside the theater and standing next to his West Coast Customs-made "Guillermobile", he answers Kimmel's questions about the latest tabloid stories by taking a rack of magazines that the "Guillermobile" has been fitted with, and attempts to interpret the stories in an amusing and mis-translated way. Another recurring joke is announcing that Rodriguez has a role in a current or recent major motion picture release and showing a clip of an at-first familiar trailer for the movie with Rodriguez edited in, his appearance often made-up to resemble a character in the movie. One sketch has Rodriguez impersonating Matt Damon's character of Jason Bourne in The Bourne Ultimatum by responding when asked to be named, "I am Yay-son... Bourne Identity." A physical fight between Rodriguez and Damon's actual character ensues. Rodriguez also starred alongside Kimmel in Boo!, a spoof of Saw. Rodriguez often sets out to interview famous celebrities. Some of his subjects do not know who he is, which the show uses for humorous interplay. Rodriguez regularly appears at the NBA Finals to interview players. At the 2015 Finals, he called out to LeBron James as James was practicing. James ignored Rodriguez, who had a meter counting how many times the name "LeBron" would be called before James acknowledged his presence. Rodriguez appeared as a special guest on the last episode of UnivisiontelenovelaEva Luna on April 11, 2011. In 2017, he had a brief uncredited role in Marvel's Guardians of the Galaxy Vol. 2 as a policeman, which he revealed in a video on Jimmy Kimmel Live! in April 2017. Rodriguez was made an honorary citizen of Dildo through the Newfoundland tradition of "screeching in," on August 15, 2019 during Jimmy Kimmel Live!
