Chicago, which has never held an Olympics, now will try to persuade the International Olympic Committee that it deserves to be the host, joining a group of bidders expected to include Madrid, Prague, Rome, Rio de Janeiro and Tokyo.
The IOC will award the 2016 Games in October 2009.
"It was a very tough decision," USOC chairman Peter Ueberroth said before opening a sealed envelope and revealing the winning city. "If I had all the power — and sometimes people accuse me of that — I would take the map and merge the two cities, because I'll tell you what: If you could take the mayors of these two communities and have them run our country, we would all be better off."
The USOC had said beforehand it would not release Saturday's vote count.
By choosing Chicago instead of Los Angeles, the 11-member USOC board of directors went with a city that does not have major venues already in place. Los Angeles held the Summer Games in 1984 — when the Olympics were run by Ueberroth — and in 1932.
Chicago, meanwhile, offered a bid that hinges on building new facilities, mostly situated around the downtown lakefront and nearby parks. The centerpiece would be an 80,000-seat, $366 million temporary Olympic stadium that would be built in historic Washington Park. Chicago's plans also call for a $1.1 billion lakefront village that would be built near the convention center just south of downtown.