In 2021, he was included on the Time 100, Time 's annual list of the most influential people in the world. More recently, Sy has signed a multi-year feature film deal with Netflix.
Lupin has become one of the most-watched non-English series on Netflix. In 2021, he starred in Netflix's hit series Lupin, a modern day retelling of Arsène Lupin novels. In 2017, he voiced the character Hot Rod in the film Transformers: The Last Knight, the fifth installment in the Transformers series. In 2015, alongside Bradley Cooper, he played a compromised chef in Burnt. He co-starred in the fourth installment of the Jurassic Park franchise, Jurassic World, which was released in June 2015. He also starred in Samba, directed by Olivier Nakache and Éric Toledano. In 2014, Sy appeared in X-Men: Days of Future Past, playing the character Bishop. On 30 December 2012, Sy was voted the favourite personality in France, based on a poll run by Le Journal du Dimanche, ahead of fellow actor Gad Elmaleh. Additionally, he won the César Award for Best Actor in 2012 for the same film. He and co-star François Cluzet were jointly bestowed the Best Actor Award at the Tokyo International Film Festival. He also received a nomination for a Satellite Award for Best Actor.
The role earned him the 2012 Globe de Cristal for Best Actor. As a result, Sy was voted third favourite French personality behind Yannick Noah and Zinedine Zidane. The film enjoyed tremendous success, topping the French box office in 2011 and becoming the best selling French film of all time in its native country, with more than 19 million tickets sold. In 2011, Sy starred in The Intouchables, playing a streetwise young man who becomes the personal care assistant to a wealthy quadriplegic (played by François Cluzet). In 2009, he voiced some of the characters of Logorama with his partner Fred Testot. In 2008, he appeared in "Bienvenue chez les Bylkas", a video clip by Sinik. He previously had also voiced a sheep in Disney's Brother Bear.
Sy then went to Los Angeles, where he lent his voice to Zip in the French version of the Tomb Raider Legend video game. He appeared in the television game show Fort Boyard in 2006. Most notably, Sy co-hosted Service après-vente des émissions, a French short comedy television series, with Testot from 2005 to 2012 on Canal+ until it was cancelled.
Following these roles, he appeared in various TV and stage shows such as Je ne fais pas mon âge and Omar et Fred: le spectacle. He then created a TV show called Le Visiophon. Afterwards, he appeared in the TV show Le Cinéma de Jamel on Canal+, with Jamel Debbouze. Sy began his career after high school in 1996, working at Radio Nova, where he met his comedy partner Fred Testot. Omar Sy winning the César Award for Best Actor in 2012 at the 37th César Awards for The Intouchables