Christopher Lambert started his career playing supporting parts in several French films, Ciao, les mecs (1979), Le bar du téléphone (1980), Asphalte (1981), Une sale affaire (1981), Putain d'histoire d'amour (1981), Douchka (1981), Légitime violence (1982), and one episode of Cinéma 16 (1982).

Around that time Director Hugh Hudson had just finished his Academy Award winning film Chariots of Fire (1981) and Warner Brothers was desperate to hire him to direct another film. After looking at all their available scripts he chose to do a film adaptation of Novelist Edgar Rice Burroughs' iconic character Tarzan, a man who was raised by gorillas in the jungle. Hudson wanted an unknown to play the part and tested many young actors. Lambert got the role partly due to his myopia, because when he took off his glasses it seemed he was always looking into the distance.

Greystoke: The Legend of Tarzan, Lord of the Apes was released in 1984 and met with great critical acclaim for both Lambert and its Director. The film was nominated for three Academy Awards and won a BAFTA Award, as well as a César Award amongst other nominations.

That same year he did Russell Mulcahy's Highlander, in which he starred as Connor MacLeod from the Scottish Highlands, known as the Highlander, one of a number of immortal warriors who can be killed only by decapitation. After initial training by another highly skilled immortal swordsman, Ramirez played by Sean Connery, MacLeod lives on for several centuries, eventually settling in New York City, running an antiques shop. In 1985, he falls in love with a police forensic scientist named Brenda. He also finds out that he must face his greatest enemy, the Kurgan, played by Clancy Brown, who wishes to kill MacLeod and to obtain "the Prize" – which gives special abilities to the last living immortal warrior, vast knowledge and power which could enslave the human race. The film became a cult hit and was an international box-office success, as well as his most famous role. The rock group Queen composed and performed the Soundtrack, and Lambert also appeared as MacLeod in the music video for Queen's "Princes of the Universe".

In 1986, he took the leading role in Marco Ferreri's I Love You. The film was nominated for the Palme d'or at the Cannes Film Festival, and was nominated for the Silver Ribbon at the Italian National Syndicate of Film Journalists.

In 1987, he starred in the troubled production of The Sicilian, directed by Michael Cimino, and based on the Mario Puzo book by the same name. He stars as Salvatore Giuliano an egocentric bandit who fights the Church, the Mafia, and the landed gentry while leading a populist movement for Sicilian independence. The studios trimmed down the director's cut of the film. It was released in 1987, and was less successful than his previous pictures, receiving a lukewarm reception by critics and being only marginally profitable. However the director's cut received better reviews upon its release in France.

Lambert was married to Diane Lane from October 1988 until their divorce in 1994. They have a daughter, Eleanor Jasmine.

In 1990, he did the comedy Why Me? co-starring Christopher Lloyd. They play burglars who get into trouble after stealing a sacred ruby from Turkey.

In 1991, Lambert reunited with Director Russell Mulcahy and Sean Connery and to make the Highlander sequel, Highlander II: The Quickening. Mulcahy didn't like the screenplay right from the start, and the production team was lured to shoot it in Argentina to reduce production costs; the country however was going through a financial crisis. Much of the script wasn't filmed and the final result is a patchwork. Its poor performance was possibly a result of the bonding company’s interference with the director; Mulcahy reportedly hated the final product so much he walked out of the film’s world premiere after viewing its first 15 minutes. For similar reasons, Christopher Lambert threatened to walk out of the project when it was nearing fruition. However, due to contract obligations, he did not.

In 1992, he appeared in four projects. The first was the suspense thriller Knight Moves, in which he was also an executive Producer, where he plays a chess grandmasters suspected of murder. He appeared in the first episode of the television show Highlander: The Series passing on the lead role to actor Adrian Paul. He also appeared in the French crime thriller Max et Jérémie co-starring Philippe Noiret and Jean-Pierre Marielle.

In 1993, he made an un-credited cameo in the comedy Loaded Weapon 1.

In 1994, saw the release of two collaborations with actor Mario Van Peebles. They played the side by side leads in the action film Gunmen, and Van Peebles was the main villain in Highlander III: The Sorcerer. In this third installment of franchise, Connor MacLeod is forced to face a new, dangerous enemy, a powerful sorcerer known as Kane who wants to gain world domination. Lambert also starred in the action film Roadflower. In France, he produced his second Patrick Braoudé film called Neuf mois which was nominated for two César. In the USA, he produced the film Dead Beat starring Bruce Ramsay.

Also in 1995, he produced Xavier Beauvois's N'oublie pas que tu vas mourir which won the Special Jury Award at the Gijón International Film Festival, won the Prix Jean Vigo, won the Jury Prize and was nominated for the Palme d'Or at the Cannes Film Festival. He was also an executive Producer on Chris Colombus' Nine Month an American remake of Neuf mois, it went on to gross $138 millions.

In 1996, he was an executive Producer and the lead in Nils Gaup' western film North Star co-starring James Caan. He played the lead in the action film Adrenalin: Fear the Rush. Finally he was one of the leads in the French film Hercule et Sherlock. That year he also produced When Saturday Comes, a football sport drama starring Sean Bean.

In 1997, he starred in Gabriele Salvatores' cyberpunk science fiction film Nirvana. The film tells the story of a virtual reality game designer, played by Lambert, who discovers that the main character of his game has achieved sentience due to an attack by a computer virus. The film was screened out of competition at the Cannes Film Festival. It went on to win one and was nominated for eight David di Donatello Awards, nominated for best film at Fantasporto, won best Director at Flaiano International Prizes, won three and was nominated for two Golden Ciak Awards, nominated for one Italian Golden Globe, and nominated for five awards of the Italian National Syndicate of Film Journalists.

In 1998, he produced and starred in two films. Operation Splitsville was a remake of Génial, mes parents divorcent which he produced several years earlier. The second was called Gideon, where he plays a man with a mental disability, who moves into a nursing home known as Lakeview, with many elderly inhabitants.

Lambert married Jaiymse Haft on 6 February 1999 but that union was dissolved. Beginning in 2007, he had been in a relationship with Sophie Marceau, with whom he appeared in La disparue de Deauville. They announced their separation on 11 July 2014.

In 2000, he played in the fourth installment of the Highlander franchise Highlander: Endgame. The film unites Adrian Paul, the actor of the series, with him. This would be last sequel Lambert appeared in. The final movie of the series cames seven years later, when Paul made Highlander: The Source in 2007.

In 2001, he played the lead role of Gallic chieftain Vercingetorix in the France-Canada production Druids. He also starred in John Glen' s The Point Men, about a team of Israeli agents being killed off one-by-one after a botched anti-terrorist operation. He also provided his voice for the English dub of the animated series Mazinkaiser.

In 2002, he was an executive Producer and a co-lead in the thriller The Piano Player, with Dennis Hooper. He also provided his voice for the English dub of the animated series Jing: King of Bandits.

In 2003, he played in Absolon a post-apocalyptic science fiction thriller film. He also played a supporting role in the French film Janis and John. He also acted in the short film Qui veut la peau de Roberto Santini?.

In 2004, he acted opposite Nastassja Kinski in the French film À ton image. He also played in one episode of Cirque du Soleil: Solstrom. He was an executive Producer on the film The Confessor starring Christian Slater, Molly Parker, and Stephen Rea. The film follows a straying Catholic priest's, played by Slater, investigation of a troubled teen's mysterious death. It was nominated for two awards at the Directors Guild of Canada.

In 2005, he acted in the television film biopic Dalida.

In 2006, he was an executive Producer and star on the film Day of Wrath. He starred in the French film Le Lièvre de Vatanen. He also played a supporting role in Richard Kelly' Southland Tales.

In 2007, he starred in the vampire film Metamorphosis. He starred in the French film Trivial directed by Sophie Marceau. It's about a police inspector, struggling with depression following his wife's death, who investigates a suspicious missing person's case at the request of a mysterious woman. During that time, he started a relationship with Marceau.

In 2008, he played in the French crime thriller Limousine.

In 2009, Lambert was a lead in Claire Denis' White Material; both the film and Lambert's performance received critical acclaim. The film stars Isabelle Huppert as a struggling French coffee Producer in an unnamed French speaking African country, who decides to stay at her coffee plantation in spite of an erupting civil war. The film has appeared on a number of critics' top ten lists of the best films of 2010. It was nominated at the Denver Film Critics Society Award for Best Foreign Language Film, for a Golden Lion, a Satellite Award for Best Foreign Language Film, at the Washington DC Area Film Critics Association, etc.

In 2010, he played in Philipp Kadelbach' Das Geheimnis der Wale. The film is about the widow of a whale researcher who joins force with an Environmentalist played by Lambert to fight an oil company. That year he also played the lead in The Gardener of God a biopic about Gregor Mendel.

Lambert wrote two novels La fille porte-bonheur in 2011, and Le juge in 2015.

Shortly afterwards, he got the of Marcel Janvier (alias "The Chameleon"), a recurring villain in award winning hit police crime TV drama NCIS: Los Angeles. His character was in 6 episodes from 2012 to 2013 — the two highest rated seasons of the show.

In 2013, he was one of the cast members in the horror film Blood Shot. He also acted in the French TV series La source.

In 2014, he played in the film Electric Slide, starring Jim Sturgess, is an American biographical crime drama about the Los Angeles-based bank robber Eddie Dodson. His co-stars included Isabel Lucas, Patricia Arquette, and Chloe Sevigny.

In 2015 he co-starred in Claude Lelouch' Un plus une, a French romantic comedy film starring Jean Dujardin, Elsa Zylberstein, and Alice Pol. He also co-starred in the film 10 days in a Madhouse, a 2015 American biographical film about the experiences of undercover Journalist Nellie Bly.

That he also played the lead villain in the film Kickboxer: Retaliation. The movie is an American martial arts film and a sequel to the 2016 film Kickboxer: Vengeance. The film stars Alain Moussi, and Jean-Claude Van Damme. It co-stars Ronaldinho, Mike Tyson and Hafþór Júlíus Björnsson. The film received stellar reviews.

In 2017 he re-collaborated with Claude Lelouch in the star studded comedy Chacun sa vie et son intime conviction. He also acted in the thriller The Broken Key with Rutger Hauer, Michael Madsen, Geraldine Chaplin, Franco Nero, and william Baldwin. He also played himself in one episode of the French TV show Call My Agent!.

Lambert plays the role of SS officer Karl Frenzel in the Russian film Sobibor by Director Konstantin Khabensky which is scheduled to be released in 2018. The film is a World War II drama about the only successful uprising in a Nazi death camp.