- Sandra Bullock gave George his break into television stardom with her own production company when she sent out a scout to check the clubs for Latino talent because there were no Hispanic shows on television.
- On April 25, 2005, he had a successful kidney transplant surgery using an organ donated by his wife, Ann Serrano Lopez.
- On October 10-12, 2003, he became one of the few comedians to be able to sell out Los Angeles' historic Universal Amphitheater for three straight nights.
- George Lopez, his character on George Lopez (2002), was ranked #18 in TV Guide's list of the "50 Greatest TV Dads of All Time" [June 20, 2004, issue].
- Turned down a role in Desperado (1995) because he does not want to be in films that promoted negative images of Latinos.
- Has had an ongoing feud for years with CHiPs (1977) star Erik Estrada, because Estrada wouldn't sign an autograph nor shake his hand when Lopez was a child while Estrada was filming an episode of CHiPs (1977) near Lopez's neighborhood. Since then, Lopez vowed to make Estrada pay.
In 2011, Estrada told a Miami radio show, The Enrique Santos Show, that he didn't remember ignoring Lopez, but that he was tired of Lopez thrashing his name and that he had seen Lopez at a church event and challenged him to a fight and that Lopez backed down, stating, "I'm a comedian, not a fighter.". - One of the many witnesses in the Michael Jackson trial.
- Only the fourth Latino ever to head a sitcom, the first three being Desi Arnaz (I Love Lucy (1951)), Freddie Prinze (Chico and the Man (1974)), and Paul Rodriguez (a.k.a. Pablo (1984)).
- Friends with Steve Harvey, Eva Longoria, Constance Marie, Oscar De La Hoya, Cedric The Entertainer, D.L. Hughley, Eddie Griffin and Charlie Murphy.
- Auditioned for a role in Blood In, Blood Out (1993).
- In 2007, Forbes magazine estimated his earnings for the year at $26 million.
- Attended and graduated from San Fernando High School in Los Angeles, California (1979).
- Was a disc jockey on MEGA 92.3 in Los Angeles, California.
- He was awarded a Star on the Hollywood Walk of Fame for Television at 6801 Hollywood Boulevard in Hollywood, California, on March 29, 2006.
- Good friends with WWE Hall of Famer Pedro Morales and Andy Garcia and his family.
- On February 27, 2014, George Lopez was arrested for public intoxication after getting drunk and falling asleep on the floor of the Caesars Windsor casino in Ontario, Canada. The casino's security alerted law enforcement upon finding him sleeping on the casino floor. Lopez had performed at the casino earlier that day in the evening. He had another show the following day, which the casino duly canceled. Soon after, a photograph of a drunken and passed-out asleep Lopez quickly circulated around the web.
- His late-night talk show, Lopez Tonight (2009), ended abruptly on August 12, 2011, before its third season began.
- Has appeared in one film that has been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically significant": Real Women Have Curves (2002).
- Has a philanthropic organization called the Lopez Foundation.
- His live comedy album, "Team Leader" (2003), was nominated for the 2004 Grammy Award for "Best Comedy Album", up against albums by Garrison Keillor, 'Weird Al' Yankovic, Margaret Cho and David Cross.
- On June 8, 2002, he hosted the Seventh Annual Florida Sports Awards from Jacksonville's Times-Union Center for the Performing Arts.
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