Miss Philippines, Janine Tugonon, came in second, while Miss Venezuela, Irene Sofia Esser Quintero, was third.
Culpo won her state contest in a rented $20 dress with a hole in it and then began working out, dieting, and studying current events on flashcards to compete for the Miss USA crown.
After her win Wednesday, Culpo told reporters she hoped to bring the country some good news in the wake of last week's deadly school shooting in Connecticut.
"It's such an honor to be representing the U.S.A. in an international beauty contest in spite of all the tragedy that's happened in this country lately," she said. "I really hope that this this will raise everybody's spirits a little."
The daughter of two professional musicians, Culpo has played the cello alongside world-renowned classical musician Yo-Yo Ma and followed in her parents' footsteps with performances at Carnegie Hall in New York City.
Her father called her the "nerdiest" of her siblings, and her brother recalled that she was "really chubby and sort of weird when she was younger."
They speculated that the same single-mindedness that helped her master the cello as a child propelled her rapid rise through the beauty pageant ranks.
As Miss Universe, Culpo will receive an undisclosed salary, a wardrobe fit for a queen, a limitless supply of beauty products, and a luxury apartment in New York City.
Copyright 2012 The Associated Press.