The story centers on the O'Leary family, pioneer settlers whose eldest boys achieve notoriety and power in bustling Chicago. After Jack (Don Ameche) gets elected mayor with the help of his popular brother Dion (Tyrone Power), the two lock horns over the future of Chicago's slums. Using his cabaret singer wife (Alice Faye) as a pawn in their dispute, Dion accelerates their intense rivalry as the whole town takes sides. It is not until a massive fire wipes out all of old Chicago that the O'Learys' lives are changed forever.

A huge-budget drama released by Fox Studios in 1937 in response to MGM's historical-disaster film SAN FRANCISCO, IN OLD CHICAGO is a fictionalized account of Chicago's Great Fire of 1871. Mrs. O'Leary's (Alice Brady, MY MAN GODFREY) two sons couldn't be more different: Jack (Don Ameche, HEAVEN CAN WAIT) is a lawyer in the running to become the mayor of the city, while Dion (Tyrone Power) is a powerful force in the less-reputable echelons of town. In addition to the divergent paths their lives have taken, the brothers are also in love with the same woman, beautiful singer Belle Fawcett (Alice Faye, HELLO, FRISCO, HELLO), whose choice between the brothers only intensifies their rivalry. The feud comes to a head just before Mother O'Leary's famous cow knocks over the fateful lantern, and in the ensuing chaos of the fire, the brothers join forces to salvage the city. Both tragedy and redemption visit the O'Leary family in a dramatic climax that features some stunning special effects footage of the consuming fire, which won the film the 1938 nomination for Best Picture.