A fiery young heiress, Ellen "Ellie" Andrews, defies her wealthy father by eloping with a fortune-hunter. When her father takes her on his yacht to have the marriage annulled, she jumps ship and flees to reunite with her new husband, finding herself an unsupervised runaway in Depression-era America. Determined to reach her husband in New York, she embarks on a bus trip, navigating a world far removed from the sheltered life she's known. Without the experience of fending for herself, Ellie's journey quickly becomes a comedy of errors as she learns the realities of life on the road.

On this journey, Ellie encounters Peter Warne, an out-of-work newspaper reporter who recognizes her as the runaway heiress plastered across the national news. Seeing a golden opportunity for a career-saving story, he takes on the role of her unsolicited protector and traveling companion, with the intention of getting an exclusive on her escapade. An odd couple in every sense, their relationship is initially fraught with antagonism. However, as they travel together, enduring various adventures and mishaps, they inevitably develop a mutual understanding and respect against the backdrop of the American rural landscape, populated by a hostes of colorful characters. Bound by necessity, but divided by class and temperament, they bicker and banter their way across the country as an unlikely bond forms between them.