The star of Jacques Audiard's vibrant Mexico-set musical "Emilia Perez" had an acting career, a wife and a daughter before she transitioned age 46, writing a book about it.
She channelled her life's experience into the film, playing both ruthless narco gangster Manitas and then title role Emilia Perez after a gender affirmation operation.
"Thank you for your creativity. You are the best director in the world," she said to Audiard after receiving the prize, which was also jointly awarded to pop star Selena Gomez, US actress Zoe Saldana and Mexican actress Adriana Paz.
"Selena Gomez, I am in love with you," she added.
With tears in her eyes, she dedicated the award to "all the trans people who are suffering".
"We all have the opportunity to change for the better, to be better people," she said.
"If you have made us suffer, it is time for you also to change."'Normal people'
Gascon told the press earlier during the festival that playing Manitas was a blast.
"I won't lie. Playing Manitas was much more fun than playing Emilia Perez," she said.
She told the press she was initially approached just to play Emilia, but lobbied Audiard until he agreed she could play Manitas too.
"I had to convince him, sending him videos and photos for months, until one morning he rang me up and said: 'Both roles are yours. Leave me alone,'" she said, laughing.
Born Carlos Gascon in the Madrid suburb of Alcobendas, the actor met her wife Marisa in a nightclub aged 19. Together they had a daughter who is now 13.
Gascon started acting in the 1990s in popular Spanish television series before moving to Mexico where the actor appeared in popular 2013 Mexican film "Nosotros los Nobles" and completed her transition.
She told the press in Cannes she had wanted to be a girl since she was four years old.
"We're normal people who can have the careers they want," said Gascon.
"Being trans is unimportant. A trans person is someone going through a transition. Once they have transitioned, that's it. They are what they are," she said.
