The Iron Man star, 49, will welcome a daughter with wife Susan Downey in November, according to a brief message posted on his Twitter page on Wednesday.
He writes: "Yo. Susan. Me. Baby. Girl. November. Scorpio?"
The actor's representative has since confirmed the news.
The couple is also parents to baby boy Exton, who was born in February, 2012.
Downey, Jr. also has a grown-up son named Indio with actress/singer Deborah Falconer.
The 20 year old hit headlines last month after he was arrested for cocaine possession in Hollywood.