US coach Mauricio Pochettino has selected Matt Freese over Matt Turner to start in goal in Friday's World Cup match at Los Angeles Stadium while Julio Enciso will make a surprise start for Paraguay despite a recent injury.
US starting lineup includes defender Chris Richards, who had been working his way back from an ankle injury.
Folarin Balogun and Christian Pulisic spearhead U.S. attack and captain Tim Ream will lead the home side's defence.
Enciso's presence should provide a boost to a Paraguay squad that has struggled to score in recent matches.
Gustavo Alfaro selects Orlando Gill to start in goal.
The Group D match marks the first match in the U.S. of the expanded 48-team World Cup.
Orlando Gill, Omar Alderete, Juan Jose Caceres, Junior Alonso, Gustavo Gomez, Diego Gomez, Miguel Almiron, Andres Cubas, Damian Bobadilla, Antonio Sanabria, Julio Enciso
Matt Freese, Sergino Dest, Chris Richards, Antonee Robinson, Tim Ream, Alex Freeman, Tyler Adams, Weston McKennie, Malik Tillman, Christian Pulisic, Folarin Balogun