Santiago was born in the Carabanchel neighbourhood in Madrid. After studying Arts at the Complutense University of Madrid, he decided to pursue a career as a filmmaker and in 1989 he directed the short Relatos de medianoche with a budget of 7000 pesetas (around US$50). In 1992 he went on to direct his first professional short Evilio, followed with Perturbado in 1993.

In 1993, he had a small role in Alex de la Iglesia’s film Acción mutante. Two years later, he starred in El día de la Bestia, from the same director and that role made him famous in Spain. In 1998 he directed the film that brought him to stardom, Torrente: El brazo tonto de la ley (1998), in which he also acted as the lead character José Luis Torrente, a sleazy crime-fighter. Its popularity led to a sequel (Torrente 2: Misión en Marbella) and a computer game (Torrente: El juego).

Torrente 2: Misión en Marbella made €22,838,500 at the Spanish box office, becoming the highest grossing Spanish film of all time. Torrente 3: El protector, the third film in the series, was released in September 2005. Its advertising campaign parodied Batman Begins, using the phrase “Torrente Acabado” (“Torrente Finished”). Although he declared Torrente 3: El protector would be the last of the Torrente series, Torrente 4 was released in 2011. In 2010, he played the title role in El gran Vázquez, based on the life of the legendary cartoonist/wastrel Manuel Vázquez Gallego.

In 2014 he released Torrente V: Operación Eurovegas with Alec Baldwin as guest star, and was the top release of 2014 in Spain.

In 2018 he appeared in the third season of MasterChef Celebrity. He was the 10th contestant to be eliminated.