Tautou caught her biggest break, though, when British actress Emily Watson dropped out of a proposed teaming with director Jean-Pierre Jeunet. After auditioning for the role of a Monmartre waitress who embarks on fixing the lives of others while neglecting her own, the charismatic and beautiful actress landed the star-making role in the whimsical "Le Fableux destin d'Amelie Poulain" (2001) which became a box-office juggernaut in France. With a shortened title, "Amelie", the film, propelled by Tautou's sly and charming turn, went on to enchant critics and audiences throughout the world.
Tautou next graced screens in a trio of French films, first as a young woman searching for love and spirituality in "Dieu est Grand, je suis Toute Petite" aka "God is Great, I'm Not" (2002), a medical student involved with a married doctor in À la Folie... pas du Tout" aka "He Loves Me... He Loves Me Not" (2002) and as part of the international ensemble of "Auberge espagnole, L'" aka "Pot Luck" (2002). Tatou's next major role was for director Stephen Frears in "Dirty Pretty Things" (2003), a dark and shadowy thriller in which she played an illegal Turkish immigrant whose morally upright lover uncovers sinister activities at the hotel where he works.
She rejoined “Amelie” director Jean-Pierre Jeunet for his next film, “A Very Long Engagement” (2004), an ambitious, if not flawed World War I drama. Tatou played a beautiful French woman with a bum leg from a childhood bout with Polio whose fiancé (Gaspard Ulliel) is caught inflicting a wound on himself in order to be sent home from the front. Along with four other ne’er-do-wells, her fiancé is marched to the hinterland between the French and German lines where the cowards are sure to be killed. Despite receiving word of her fiancé’s death, she knows deep down he’s still alive and hires a private detective (Ticky Holgado) to find him after the war. Tatou was next set to appear in one of the most controversial and anticipated movies to have come along in decades, “The Da Vinci Code” (2006), directed by Ron Howard from Dan Brown’s mega-blockbuster about a secret religious society that has spent the past 2000 years guarding a secret that could destroy the foundations of society if it were revealed.