The Big Bus follows the maiden non-stop trip of Cyclops, a state-of-the-art nuclear-powered bus named after its single large headlight. Coyote Bus Lines' Dan Torrance, a down-on-his-luck driver with a reputation for eating his passengers, is recruited to drive the massive vehicle across America. As the bus embarks on its historic journey from New York to Denver, it faces various disasters and sabotages, including a bomb hidden by Alex, an accomplice of the sinister Ironman.