Penelope Cruz wins best actress in Venice
It was a surprisingly political turn for the flamboyant filmmaker, exploring the trauma of the 1930s Spanish civil war alongside the tale of two mothers sharing a maternity ward.
It marks a departure into dark historical territory for the director, while still focusing on the themes of motherhood and female relationships that have been central to many of his films.
Cruz described Almodovar as "my safety net" in a press conference ahead of their red carpet appearance in Venice.
"He can ask me to do something that can really scare me but I know he will be there waiting to sustain me," she said, adding that she was grateful to the director for giving her "so many different, challenging characters".
Cruz has appeared in seven of Almodovar’s movies, including "All About My Mother" and "Volver".
She had a busy fortnight in Venice, also starring in the well-received "Official Competition", a comedy about ego-maniacs in the film business that saw her in a rare appearance alongside her Spanish megastar Antonio Banderas.
Born in Madrid in 1974, she appeared destined for a career in the entertainment, initially studying ballet at Spain’s National Conservatory before winning an acting competition that led to roles on TV and in music videos.
Her break into film came in Spanish director Bigas Luna’s "Jamon, Jamon" in 1992, which received critical acclaim and was notable for its erotic scenes featuring a 16-year-old Cruz and Javier Bardem, who would much later become her husband.
That was followed soon afterward by "Belle Epoque", which won the Oscar for best foreign film, and featured Cruz as one of four sisters vying for the love of an army deserter.
The next milestone came in 1997, when she was cast in her first film by Pedro Almodovar.
"Live Flesh" marked the beginning of a decade-long collaboration between Almodovar and the actress which has included roles in another foreign language Oscar-winner, 1999’s "All About My Mother".
Cruz struggled to establish herself in mainstream Hollywood.
She achieved a rare but unwanted feat in 2001 when she received three nominations in the "Golden Raspberries" Oscars spoof for "Captain Corelli’s Mandolin," "Blow" and "Vanilla Sky".
The latter cast her alongside Tom Cruise, whom she ended up dating for three years.
Other flops followed including "Gothika" and "Sahara".
But she bounced back, picking up an Oscar nomination for the 2006 Almodovar film "Volver".
And she made history by becoming the first Spanish actress to win an Oscar in 2009 for her part in the Woody Allen comedy "Vicky Cristina Barcelona".
She was again paired with Bardem in that film, triggering a romance that led to their marriage in 2010.
The fiercely independent Cruz is also wary of being type-cast simply for her striking physical beauty.
"The most difficult thing in the world is to start a career known only for your looks, and then to try to become a serious actress," she has said.
"No one will take you seriously once you are known as the pretty woman."