Banderas, the son of a police officer and a teacher, was a soccer protégé as a youth, but a serious foot injury at age 14 dashed his hopes of making the sport his profession. The following year he developed an interest in acting after seeing a stage performance of the rock musical Hair. In 1981 he embarked on a five-year acting stint with the Spanish National Theatre in Madrid. There he was discovered by movie director Pedro Almodóvar, who began offering him roles. In his first movie with Almodóvar, Laberinto de pasiones (1982; Labyrinth of Passion), Banderas received good notices for his role as a gay Islamic terrorist. Under Almodóvar's direction, the young actor was able to express his talent fully through such unconventional roles as rapist, mental patient, and kidnapper.

Banderas moved to Hollywood in 1989 and three years later appeared in the cult favourite The Mambo Kings, playing a young Cuban musician living in New York City. Although he spoke almost no English, Banderas was able to learn his lines phonetically and later took intensive English courses, which helped him land the role of Tom Hanks (Hanks, Tom)'s lover in the box-office hit Philadelphia (1993). Banderas subsequently appeared in a series of English-language films, including The House of the Spirits (1993); Interview with the Vampire (1994), an adaptation of Anne Rice's novel that also featured Tom Cruise (Cruise, Tom) and Brad Pitt; Miami Rhapsody (1995); Robert Rodriguez's Desperado (1995), in which Banderas played El Mariachi, a gun-toting musician; and Assassins (1995). In 1996 he costarred with Madonna in the musical Evita (1996), playing the role of Ché, the film's narrator. Accused by some critics of overexposure, Banderas conceded that he was ambitious but said that in Spain actors prove their success in this manner.

Banderas's unique screen persona, equal parts machismo and sensitivity, was further showcased in the successful The Mask of Zorro (1998), which costarred Catherine Zeta-Jones (Zeta-Jones, Catherine), The 13th Warrior (1999), and Play It to the Bone (1999). He made his directorial debut with the comedy Crazy in Alabama (1999), which starred his second wife, actress Melanie Griffith. In 2001 Banderas reteamed with Rodriguez on Spy Kids, playing a family man who is forced to return to his former career as a secret agent. The movie was a hit and led to several sequels. Banderas later reprised the role of El Mariachi in Rodriguez's Once Upon a Time in Mexico (2003), and he provided the voice of Puss in Boots in the popular Shrek sequels (2003, 2008). In 2005 he starred in The Legend of Zorro, a sequel to The Mask of Zorro. The following year Banderas directed his second film, El camino de los ingleses (Summer Rain), an adaptation of an Antonio Soler novel about a group of teenage boys who have a memorable summer vacation.