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The son of a highly respected music professor, Florenz "Flo" Ziegfeld, Jr. (Powell) yearns to make his mark in show business. He begins by promoting Eugen Sandow (Nat Pendleton), the "world's strongest man", at the 1893 Chicago World's Fair, overcoming the competition of rival Billings (Frank Morgan) and his popular attraction, belly dancer Little Egypt, with savvy marketing (allowing women to feel Sandow's muscles).
Later, on an ocean liner to England, Flo runs into Billings again and discovers that he is on his way to sign a beautiful French star, Anna Held (Rainer), to a contract. Despite losing all his money gambling at Monte Carlo, Flo charms Anna into signing with him instead.
At first, Anna is not a success. However, Flo manages to generate publicity by sending many gallons of milk to Anna every day for a fictitious milk bath beauty treatment, then refusing to pay the bill. The newspaper stories soon bring the curious to pack his theater. Flo and Anna then get married.
However, one success is not enough for the showman. He has an idea for an entirely new kind of show, one that will "glorify" the American woman. Thus, the Ziegfeld Follies is born, a lavish production filled with beautiful women. This makes Anna very nervous, as she is still performing in her own show and will be unable to keep an eye on her husband. It is a smash hit, and is followed by more versions of the Follies. Soon Flo hires Fanny Brice (playing herself) away from vaudeville and gives stagehand Ray Bolger (also playing himself) his break as well.
He also tries to make a star out of Audrey Dane (Virginia Bruce), but alcoholism turns out to be her downfall. However, a short time before, Anna becomes jealous of the attention Flo pays to Audrey and divorces Flo. Afterward, Flo meets Broadway star Billie Burke ([Loy) and marries her. When she hears the news, a heartbroken Anna telephones Flo and pretends to be glad for him. Flo and Billie eventually have a daughter named Patricia.
Flo has more hits, but after a while, the public's taste changes, and people begin to wonder if the times have not passed him by. Stung, he vows to have four hits on Broadway at the same time. He achieves his goal - one of those four hits being Show Boat (1927) - but then the stock market crash of 1929 bankrupts him, forcing Billie to go back on the stage.
Shaken by the reversal of his financial fortunes and the growing popularity of movies over live stage shows, he becomes seriously ill. In the final scene, in a half-delirium, he recalls scenes from several of his hits, exclaiming, "I've got to have more steps", a remark he made several times when examining the set designs of his Ziegeld Follies, before slumping over dead in his chair.