The funny man made the announcement during an appearance on "The Ellen DeGeneres Show."
"This is the first time I've said anything," he said during the interview, which airs Monday. "We're very excited."
He said his wife, Kyla, a real estate agent, is due Aug. 5.
The couple married in January 2010 and had their first child, daughter Locklyn Kyla, in December, People magazine said Friday.
"It gives you a different purpose," Vaughn said after the birth of his daughter, who is now 2. "I feel so grateful."