The duo are searching for the legendary Tree of Life, which is believed to have healing powers. The submarine is being captained by Jesse Plemons, a villainous German who fires a torpedo at Johnson and Blunt's boat.
Johnson and Blunt also encounter mythical creatures and Johnson must battle a tiger during the adventure.
Jungle Cruise, inspired by the classic Disneyland and Walt Disney World theme park ride of the same name, is coming to theaters on July 30. Viewers can also watch the film through Premier Access on Disney+.
Jaume Collet-Serra serves as director. Co-stars include Edgar Ramírez, Jack Whitehall and Paul Giamatti.
Blunt will next be seen in A Quiet Place Part II, which hits theaters on Friday. Johnson will star as the titular character in DC Comics' Black Adam, also from Collet-Serra.