Romney took part in 19 debates during the campaign for the Republican primary early in the year. The president has not been onstage with a political opponent since his last face-to-face encounter with Arizona Sen. John McCain, his Republican rival in 2008.
Obama and Romney prepared for the evening with lengthy practice sessions. Romney selected Ohio Sen. Rob Portman as a stand-in for the president; Obama turned to Massachusetts Sen. John Kerry to play the Republican role.
The two presidential rivals also are scheduled to debate on Oct. 16 in Hempstead, N.Y., and Oct. 22 in Boca Raton, Fla.
Vice President Joe Biden and Republican Rep. Paul Ryan of Wisconsin have one debate, Oct. 11 in Danville, Ky. Both men have already begun holding practice sessions.
Associated Press writer Kristen Wyatt contributed to this story. David Espo reported from Washington.