A brief statement issued Monday by publicist Ina Treciokas says the comedian and his wife Ann came to the decision together and the breakup will be amicable.
It did not offer further details, other than to say the pair would remain business partners in a charitable foundation.
Court records did not indicate the couple had filed a petition for divorce or legal separation.
The 49-year-old comedian hosts the late-night talk show "Lopez Tonight" on TBS.
Ann Lopez donated a kidney to her husband in 2005.
The pair have a teenage daughter.
The split was first reported by celebrity website TMZ.com.