Malik Zidi was born in Châtenay-Malabry to a Kabyle Algerian father and a Breton mother. He spent his formative years in Saint-Maur-des-Fossés, a suburb of Paris. Zidi left conventional schooling early to focus on a career in comedy. After courses at the Théâtre Véronique Nordey and the Théâtre de Proposition in Paris, he briefly studied acrobatics and mime at the Théâtre de la Piscine and film at Studio Pygmalion. Zidi's first film appearance was in the 1998 film Open Bodies, directed by Sébastien Lifshitz.

In 2000, Zidi was chosen by director François Ozon for the role of the tormented, lovestruck, bisexual young man Franz in the Teddy Award-winning film Water Drops on Burning Rocks (French: Gouttes d'eau sur pierres brûlantes). The film is based on the play Water Drops on Burning Rocks by German film director and screenwriter Rainer Werner Fassbinder. It is a four-part comedy-drama, shot entirely on one set and featuring only four actors: Zidi, Bernard Giraudeau, Ludivine Sagnier and American actress Anna Levine. Zidi's role in Water Drops on Burning Rocks earned him the first of four César Award nominations.

Malik Zidi went on to roles in the 2002 film One Moment of Happiness, directed by Antoine Santana, alongside Isild Le Besco, earning a second César nomination for Most Promising Male Newcomer. In 2004 he appeared in André Téchiné's romantic drama Changing Times as Sami, the bisexual son of Cécile (played by Catherine Deneuve), who comes to his parents in Tangier to visit his Moroccan boyfriend. The film also starred actor Gérard Depardieu, and it was nominated for a Satellite Award. Zidi received his third César nomination.

In 2006, Zidi appeared in Emmanuel Bourdieu's drama Poison Friends. The film was shown at the Cannes Film Festival, and Bourdieu received the Grand Prize of Critics' Week and the Grand Prize of the Golden Rails. The film also received the SACD Prize for its screenplay, and Zidi was again nominated for a César, winning the award for Most Promising Male Newcomer in 2007.