At the age of twenty, Trintignant moved to Paris, France to study drama, and made his theatrical debut in 1951 going on to be seen as one of the most gifted French actors of the post-war era. After touring in the early 1950s in several theater productions, his first motion picture appearance came in 1955 and the following year he gained stardom with his performance opposite Brigitte Bardot in Roger Vadim's And God Created Woman.

From a wealthy family, he is the nephew of race car driver, Louis Trintignant, who was killed in 1933 while practicing on the Péronne racetrack in Picardie. His other uncle, Maurice Trintignant (born 1917), was a Formula One driver who twice won the Monaco Grand Prix as well as the 24 hours of Le Mans. Raised in and around automobile racing, Jean-Louis Trintignant was the natural choice of film director Claude Lelouch for the starring role of race car driver in the 1966 film, Un homme et une femme, a global success that made him an international star.

Trintignant’s acting was interrupted for several years by mandatory military service. After serving in Algiers, he returned to Paris and a very successful career. Subsequent leading roles in art-house classics such as Un homme et une femme (A Man and a Woman) (at the time the most successful French film ever screened in the foreign market), Bertolucci's The Conformist, and the 1969 political thriller Z, in which he portrayed an idealistic young attorney, garnered him an international following as well as the Best Actor award at the 1969 Cannes Film Festival.

He married Nadine Marquand, herself an actress as well as a screenwriter and director. Since divorced, they had a daughter, Marie (January 21, 1962-August 1, 2003), who at the age of 17 years of age performed in La Terrasse alongside her father and had become a very successful actress in her own right.

Throughout the 1970s Trintignant starred in numerous films and in 1983 he made his first English language feature film, Under Fire. Following this, he starred in François Truffaut's final film, Vivement Dimanche!

In the late 1980s and early 1990s, Trintignant worked infrequently because of health problems (consecutive from a car accident) and a growing lack of interest for movies. His 1994 role in the late Krzysztof Kieślowski's last film, Three Colors: Red marked a rare appearance for him but still earned him a César Award nomination for Best Actor.

The following year he lent his voice to the widely acclaimed La Cité des Enfants Perdus, and has made films only occasionally since. He has focused essentially on his stage work.