There are some 500 competitors representing 14 countries from around the world taking part in 10 events, including wheelchair rugby, archery, and powerlifting. The Invictus Games are the only international competition of its kind for injured veterans.
"Mark my words, you will be inspired, you will be moved, and you will be entertained," Prince Harry told the crowd at the opening ceremony at ESPN Wide World of Sports.
Obama joined the prince on the stage, alluding to the fun rivalry that has played out on Twitter between them in the lead-up to the games.
"I have asked the U.S. team not to win too much ... it's the least we can do, right?" Obama joked about the U.S.-U.K. rivalry.
"Over the past five years, I have had the privilege of meeting so many of you, and like Prince Harry, I am so incredibly inspired by all of you," the first lady said. "I am inspired by your courage, your love of country, the sacrifices you all make every day."
The Invictus Games will continue through Thursday, May 12, with coverage on ESPN2 and ESPN3.