He gave over 400 performances of L'Année du bac, by José-André Lacour, on the Parisian stage (starting in 1958).
He was given his first juvenile film roles by Italian director Valerio Zurlini.
He appeared alongside Claudia Cardinale in the romantic comedy La Ragazza con la valigia and Marcello Mastroianni in Family Diary. He then played several roles in films of Henri-Georges Clouzot (The Truth in 1960) or Mauro Bolognini (Corruption in 1963) and leading roles in four films by Pierre Schoendoerffer : La 317e Section (1965), Le Crabe-tambour (1977), A Captain's Honor (1982) and Là-haut, un roi au dessus des nuages (2004). He played in two musical movies by Jacques Demy : The Young Girls of Rochefort (1967) and Donkey Skin (1970), both with Catherine Deneuve. He also was the adult Salvatore in the international success Cinema Paradiso.
In 1966, he won two Best Actor awards at the Venice Film Festival, for the Italian film Almost a Man and the Spanish film The Search.
At 27, he created a film production company and produced and acted in Z, directed by Costa-Gavras and starring Jean-Louis Trintignant, Yves Montand, and Irene Papas. Z received the Best Foreign Film Oscar in 1969.
He produced Costa-Gavras's films État de Siège (State of Siege) in 1973 and Section spéciale in 1975. Both had political themes, and as a producer, Perrin continued along this path with a documentary on the Algerian uprising (La guerre d'Algérie) and a film on the Chilean presidency of Salvador Allende (La Spirale). In 1973, Perrin produced the first film by Benoît Lamy, Home Sweet Home in which he starred alongside Claude Jade as his love interest. The movie received 14 international awards.
In 1976, he produced another Oscar-winning film : La Victoire en chantant (Black and White in Color) by director Jean-Jacques Annaud. A year later, he embarked on Le Désert des Tartaresas a producer and an actor, co-starring Trintignant again, but also Max von Sydow, Vittorio Gassman and Philippe Noiret. The film won the Grand Prix du Cinéma Français.
Perrin then devoted himself to nature documentary. He was the producer of Microcosmos in 1995 and producer and co-director of Le Peuple Migrateur (Winged Migration) in 2001, Océans in 2009 and Seasons in 2015.
He played the role of the old Pierre Morhange, narrator of the internationally successful film The Chorus, that he also produced. The young Pépinot was played by his son Maxence.
In 2016, he received the prestigious Prix du Cinéma René Clair from the French Academy.