Jurgen Klinsmann's squad will prepare for the Gold Cup with a friendly against its CONCACAF rival in Southern California.
The match will be the squad's final tune-up for the Gold Cup, as the Stars and Stripes begin group play against Belize on July 9.
"This is a very important opportunity for us to get in a good game before the start of the Gold Cup," said U.S. head coach Jurgen Klinsmann in a statement. "It is our goal to win the tournament, and the chance to play Guatemala will be good preparation for our group. We are thrilled to get back to San Diego which has such an outstanding soccer tradition."
This is the first game for the Yanks in San Diego since 2006. The team will be looking for its first ever victory in the city, having posted an 0-5-2 record all-time.
The U.S. has a 13-4-6 record against Guatemala, dating back to 1977. The Yanks have never lost to the Chapines at home, with a 11-0-1 record.