The actress was celebrated for her performance in West Side Story.
The star, 31, collected her gong dressed in red Valentino trousers and a crop top and said her win was proof that “dreams do come true”.
DeBose won the Oscar for her performance as Anita in the classic musical, 60 years after her predecessor in the role, Rita Moreno, earned the statue herself.
DeBose added: “Now you see why Anita says I want to be in America because even in this weary world that we live in dreams do come true and that’s a heartening thing right now.”
On the production, she added: “It was the summer of a life time and I am the most privileged and grateful to have spent it with all of you.”
“My God thank you Steven Spielberg, you’re stuck with me now.”
The actress also paid tribute to Moreno, saying she “paved the way for tonnes of Anitas like me”.
Concluding her speech, DeBose added: “Imagine this little girl in the back seat of a white Ford Focus.
“Look into her eyes, you see an openly queer woman of colour, an Afro-Latina, who found her strength in life through art.
“And that’s what we’re here to celebrate.
“So to anyone who has ever questioned your identity or you find yourself living in the grey spaces…I promise you this, there is indeed a place for us.”
Eight Oscars were presented in a pre-recorded segment of the show, which will be edited into the final telecast.
Dune collected four gongs, for sound, editing, production design and score for composer Hans Zimmer.
Zimmer celebrated his win from Amsterdam, where he is on tour.
He shared a photo on Twitter of himself in a bathrobe with his statue and wrote: “It’s 2am in Amsterdam, and my daughter @zoezimmer woke me up to go the hotel bar. Wow!!”
The Long Goodbye, starring Riz Ahmed, won best live action short, while The Windshield Wiper won best animated short and The Queen Of Basketball won best documentary short.
The Eyes Of Tammy Faye won the Oscar for makeup and hairstyling.
Tennis stars Venus and Serena Williams opened the Oscars by introducing a performance of Beyonce’s nominated song Be Alive from the movie about their father, King Richard, which she delivered from a tennis court in Compton.
She was flanked by dancers and an orchestra all dressed in the colour of tennis balls.
Hosts Amy Schumer, Wanda Sykes and Regina Hall kicked off the ceremony with Sykes joking the ceremony was “where movie lovers unite and watch TV”, while Schumer added the Academy had “hired three women to host because it’s cheaper than hiring one man”.
She added she was “representing unbearable white women who call the cops when you get a little too loud”.
Hall also referred to the choice to move eight categories to a pre-recorded segment, saying it was “a controversial and difficult decision but I think we’ve moved on”, as the lights flickered on and off on the stage.
The Oscars are being held at the Dolby Theatre in Los Angeles, where Benedict Cumberbatch, Olivia Colman and Sir Kenneth Branagh are among the nominees.