Watling began her acting career in theatre and made her big screen debut when she was 15 with Jardines colgantes by Pablo Llorca. After that she participated in several TV series, such as Hermanos de leche, Farmacia de guardia or Querido Maestro, but her most successful role was in the series Raquel busca su sitio with Cayetana Guillén Cuervo. In 1998, she was nominated for a Goya award for her role in La hora de los valientes, and was named as one of European films 'Shooting Stars' by European Film Promotion in 1999. In 2002, she was nominated again for a Goya for her role in A mi madre le gustan las mujeres.

Watling dubbed Anne Hathaway as the voice of "Red Pucket" (Little Red Riding Hood) in Hoodwinked (2005). She also took part in The Oxford Murders, alongside Elijah Wood and John Hurt.

In 2006, Watling starred in Paris, Je T'aime segment "Bastille" as Marie Christine. The film was directed by many famous Directors who each had to produce a five-minute film set in Paris, the city of love. Spanish writer-director Isabel Coixet wrote and directed the segment "Bastille" and Watling starred alongside Sergio Castellitto and Miranda Richardson as Sergio's younger lover with whom he plans to run away after ending his relationship with his wife Miranda.

Watling is in a relationship with Oscar-winning Uruguayan musician Jorge Drexler, with whom she has a son, Luca, born in January 2009, and a daughter, Lea, born in July 2011.

She appears in TV series Pulsaciones, broadcast since January, 2017.