A representative for the 46-year-old actor confirmed a report Wednesday on People magazine's website. The baby is due early next year.
The couple were married in 2005. They met on the set of the film "Gothika," which Susan co-produced.
Downey has a teenage son, Indio, with ex-wife Deborah Falconer.
He received Oscar nominations for his roles in "Chaplin" and "Tropic Thunder." His film credits also include "Sherlock Holmes" and the "Iron Man" films.