Melania Trump is planning to lead the US delegation to the Invictus Games in Toronto in September.
It will be her first solo excursion outside the United States.
The First Lady, who has accompanied husband Donald Trump on the three foreign trips he has taken so far this year, said she was honoured by the opportunity.
Prince Harry founded the Invictus Games for wounded active duty service members and veterans in 2014.
More than 550 people from 17 countries are expected to compete in 12 sports in this year's games, which run from September 23 to 30.
Mrs Trump said she has been "heartened by the great success" of the Games. London was the setting for the first competition in 2015, followed by Orlando, Florida, last year.
She said: "In just two short years, the Invictus Games have allowed thousands of injured and wounded servicemen and women from many different countries to participate in adaptive sports competitions, something that should be lauded and supported worldwide."
Adaptive sports are sports that are modified for people with disabilities.
Jill Biden, wife of then-vice president Joe Biden, led the US delegation to the inaugural games in London as part of a military initiative she led with Michelle Obama, the former first lady.
Mrs Obama helped kick off the 2016 games in Orlando.