A bold and vibrant American man enters Gamages department store and pressures a young shop girl to do the unthinkable: empty her stock of fine leather gloves onto the counter. He's Harry Gordon Selfridge, an American entrepreneur preparing to open his own department store, doing market research about how to shake up shopping and reform retail. He departs, leaving a gift of red leather gloves and his business card for the shop girl, Agnes Towler, not knowing that his actions have led to her dismissal.
Harry is toiling away at building Selfridges, one of the world's finest department stores. But a massive advertising campaign and other reckless costs earn him disdain from the British press and cause his conservative business partner to pull out. Undeterred, Harry finds a savvy ally in London Evening News reporter Frank Edwards, one of the best-connected men in London. Frank does not disappoint. He provides introduction to a formidable, shrewd and powerful socialite, Lady Mae Loxley, who secures Harry the necessary investor: her (absent and cuckolded) husband. Though troubled by being in Lady Mae's debt, Harry is now able to finance his operation, and Selfridges is born.
Edwards also introduces Harry to the beautiful Gaiety dancer, Ellen Love. Their relationship, charged with immediate chemistry, is at first professional for the self-professed family man. Harry hires Ellen to represent the store as "The Spirit of Selfridges." Harry's mother, Lois, his wife, Rose, and their four children have arrived from Chicago, and despite a powerful attraction between him and Ellen, Harry wants to reform and reject his vices – gambling and girlfriends –in favor of his much-loved wife and children.
At the store's helm is Selfridge's chief of staff, Mr. Grove, a quietly intimidating man with an invalid wife at home. When Agnes, now impoverished, appeals to Harry for a job, he hires her as senior accessories sales girl. This irks Mr. Grove and Selfridge's disciplinarian head of accessories, Miss Mardle. But they become concerned about more than Agnes' qualifications when she witnesses the two sharing an intimate moment outside of Selfridges. Long engaged in love affair, they are unable to be together because Grove cannot leave his sick wife. Grove even fears blackmail when Agnes asks him to hire her hardworking but dim brother, George. What they don't know is that Agnes' strong morals would never allow her to exploit anyone; she is simply trying to raise herself and her brother and become independent of their abusive father, Reg Towler.
Meanwhile, in Selfridges' Palm Court restaurant, an ambitious waiter, Victor Colleano, is advised by his manager, Mr. Perez, that a handsome and charming man like himself would do well to make the ladies happy. Sure enough, a rich customer soon propositions Victor. But he has eyes only for Agnes, whom he sees as an ambitious professional on the move in the world, like himself. However, though they are friends, Agnes is more interested in her work, particularly in Selfridges' magnificent windows. Marvels to behold, the windows are designed by Harry's longtime creative partner, the talented and handsome Parisian Henri Leclair. But Harry's creative partnership with the designer is tested when Ellen Love undermines Henri's work, rejecting his "Spirit of Selfridges" photographs as conservative and old fashioned, and Harry sides with her. Just as Harry is executing a top-secret, inspired campaign to bring customers into his store – a grand exhibition featuring French aviator Monsieur Blériot and his airplane, the first ever to cross the English Channel – Henri quits.
But Harry has more to worry about than his temperamental window designer. His wife, Rose, dutifully spending time at home with the family, has noted her husband's increasing absence. When Lady Mae drops in uninvited, she needles Rose about Ellen Love and Harry's absence. Rose, a former painter, heads out to London's National Gallery undaunted, and there meets a handsome painter who, struck by her beauty and stillness, had been sketching her. Rose accompanies the painter, Roddy, back to his studio, but she had misunderstood his invitation. When he kisses her, she rushes away.
Harry apologizes to Henri, who decides to stay at Selfridges. As thousands of customers flood the store to see Blériot and his famous airplane, Ellen Love poses in all her glory astride the plane and Harry, buoyant from his success, lavishes his attentions on Rose. But Rose, humiliated by Ellen's flaunting of her relationship with Harry and fresh barbs from Lady Mae, leaves the celebration early.
Later, a surprise arrives for Ellen, who was caught with Harry in a compromising position in her dressing room: a key to her very own posh new flat. But for Agnes and George, no such comforts await at home, only their threatening father Reg, who has tracked them down and wheedled his way back into their lives.