The two-hour event in Orlando, Florida, included performances by British singer James Blunt and soprano Laura Wright.
Actor Morgan Freeman and former president George W Bush honorary chairman of this year's games sat in the audience for the ceremonial start of the games at Disney's ESPN Wide World of Sports Champion Stadium.
Nearly 500 athletes from 14 different countries are competing in the Paralympic-style sports competition over a four-day period beginning Monday.
"I can't tell you how proud I am to have the second Invictus Games open in America," Prince Harry said. "I'm a long way from London tonight, but when I look out, I see so many familiar faces, servicemen and women, their friends and their families and all of the people who got them here. I feel like I'm at home."
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"I served along soldiers from all over the world," Prince Harry said. "I saw the sacrifices you and your families made to serve your nations. I learned about the importance of team work and camaraderie in the way that only military service can teach you."
There was a military flyover and the black and yellow "I Am" flag, which has become the symbol of the Invictus Games, was flown by helicopter into the stadium. There was also a fireworks show.
"I want to, of course, start by thanking Prince Harry for his outstanding leadership and for bringing the Invictus Games here to Orlando. He is truly our Prince Charming. He should be proud of his work.