Ann Serrano Lopez cited irreconcilable differences in the petition, filed Tuesday in Los Angeles Superior Court. She is seeking spousal support and primary custody of their 14-year-old daughter Mayan with visitation for George, according to the site.
The couple had been married for more than 17 years.
"The decision is amicable and by mutual agreement," Lopez's rep said in September. "They remain dedicated parents, and committed partners in business and their philanthropic organization, the Lopez Foundation."
Ann famously donated one of her kidneys to George, 49, in 2005. The pair later founded the Ann and George Lopez Foundation to raise awareness about kidney disease.