Reno was born Juan Moreno y Herrera Jiménez (also written as Don Juan Moreno y Herrera Jimenez) in Casablanca, Morocco. His Spanish Andalusian parents were natives of Sanlúcar de Barrameda and Jerez de la Frontera, and had moved to North Africa to escape the dictatorship of Francisco Franco. Reno moved to France at the age of seventeen. His mother died when he was an adolescent. Reno is a former student of the Cours Simon. He was raised Catholic.

Due to his tall, hulking frame (6' 2"), he mostly played villainous brutes early on in his career. Thanks to his skills as an actor, he has broken away from this stereotype and has played everything from romantic-comedy leads to action heroes. Reno's career began in French cinema, where he appeared in many of Luc Besson's films, including Besson's first short film, L'Avant dernier. The two have continued to work together throughout their careers, in films produced, written or directed by Besson, though the films in which he has done all three have proven to be the most popular, including Nikita (1990), and the English-language films The Big Blue (1988), and Léon (1994) (known as The Professional in the United States) featuring a young Natalie Portman Additionally, he dubbed over the character of Mufasa in the French-language version of The Lion King, a role originally occupied by James Earl Jones.

Reno has starred in such high-profile American movies as French Kiss (1995) with Meg Ryanand Kevin Kline Mission: Impossible (1996) with Tom Cruise, Ronin (1998) with Robert De Niro, and Godzilla (1998), for which Reno turned down the role of Agent Smith in the The Matrix. He has not neglected to continue making French productions either - e.g., Les Visiteurs (1993) (which was later remade in English as Just Visiting in 2001) and The Crimson Rivers (2000). In 2006, he had a prominent role in the remake of The Pink Panther, playing Gilbert Ponton, the partner of Inspector Clouseau opposite Steve Martin and also portrayed Captain Bezu Fache in the Ron Howard film The Da Vinci Code.

On July 29, 2006 the actor married model and actress Zofia Borucka, 35, at the city hall of Baux-de-Provence in southern France. The French President (at the time being Presidential candidate) Nicolas Sarkozy was his best man. He was married twice before and has four children, two from each marriage. He is a huge fan of Elvis Presleyand can actually imitate Elvis' voice. He used his impression in a scene of the film Godzilla when the script needed his character to pass as an American.