The match will be played at the Allegiant Stadium on July 30 and is the second fixture of the tour, after United announced in March they will face non-league Wrexham in San Diego on July 25.
"We have worked with the manager and his staff to provide a mix of competitive opponents to play during our tour of the U.S. and we look forward to the match against Borussia Dortmund," Man United football director John Murtough said.
"As well as gaining valuable playing time, the squad will also be participating in training camps within the best sporting facilities available, giving our players the opportunity to build fitness before the start of the new Premier League season.
"The response we have received from fans since announcing we will be returning to the U.S. has been incredible. We already have a full house for the match in San Diego and I am sure it will be the same for this fixture in Vegas."
"I think back with great pleasure to the summer of 2016 when we played Manchester United in front of a large crowd in Shanghai at the time," Dortmund managing director Carsten Cramer said.
"Now we look forward to returning to North America, where the market is becoming increasingly important in the run-up to the 2026 World Cup and the enthusiasm for football is growing.
"Not only does the Allegiant Stadium look great from the outside, but the enthusiastic fans in the USA, who we have missed since our last visit, will ensure that the game in Las Vegas will hold a special place in BVB's history."
Information from Reuters was used in this report.