The actor filed divorce papers Thursday in Los Angeles, citing "irreconcilable differences."
The couple has a two-year-old daughter, Marina, who suffers from a rare brain disorder, which can cause seizures.
LeBlanc is also the stepfather to his wife's two older children from an earlier marriage, Tyler, 13 and Jacquelyn, 10.
According to court papers, the couple split on January 1, around the time LeBlanc's sitcom Joey was put "on hiatus."
A statement that was issued on behalf of the couple said, "Melissa and Matt LeBlanc have decided to end their marriage of three years.
"The dissolution is amicable. They remain devoted parents and friends. For the sake of their family, they ask that their privacy be respected at this time."
The pair was married in a romantic beachfront ceremony in Hawaii in May 2003.
LeBlanc publicly apologized to his wife and baby daughter last year, after drunkenly groping a stripper during a private lap dance.
The star admitted he got "carried away" when he visited a strip club during a 10-day motorbike trip in Canada saying, "I acted like a fool in allowing myself to be led astray and placed in such a horrible situation. I feel ashamed."
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