Mercedes Milá was born in Esplugues de Llobregat, the daughter of José Luis Milá Sagnier, Count of Montseny, and eldest of six brothers and sisters  (including newscaster Lorenzo Milá). She studied journalism and arts in Barcelona. Shortly afterwards she began working in the newsrooms of Spanish public broadcaster TVE. She joined the sports division, where she remained between 1974 and 1978, when she was selected to co-host, along with Isabel Tenaille, the talk show Dos por Dos ("Two by Two"). After the show was cancelled, Milá returned to radio. She worked with Iñaki Gabilondo in Cadena SER.
Milá's TV comeback came in 1982 with the program Buenas Noches ("Goodnight"), which became one of the hits of the season and lasted until 1984. Her personal style and directness with her guests helped her turn into one of the most popular Spanish TV personalities of the 1980s. After a brief stint with the Catalan television station TV3, and then back in TVE in 1990, she moved over to new private TV network Antena 3 in the early nineties, where she stayed until moving to private broadcaster Telecinco in 2000.
In 2000 she found renewed success as the host of the Spanish franchise of hit reality show Gran Hermano, earning poor critical reviews but massive ratings. As of 2010, Milá has hosted or co-hosted eleven of the fourteen seasons of the show (all except for season 3 in 2002, which was hosted by Pepe Navarro).