"I'm the least qualified man here tonight," Biden joked as the star-studded audience rose to their feet for a standing ovation.
Before introducing Lady Gaga's performance of "Til It Happens to You," the nation's second-in-command advocated for survivors of sexual assault.
"Good evening and thank you very much. Despite significant progress over the last few year, too many women and men, on and off college campuses, are still victims of sexual abuse and tonight I am asking you to join million of americans including me, President Obama, the thousands of students I've met on college campuses and the artists here tonight to take the pledge," Biden said.
"A pledge that says – I will intervene in situations when consent has not or has not been given. Let's change the culture. We must and we can change the culture. So that no abused womam or man, like the survivors you will se tonight, ever feel they ever have to ask themselves 'what did i do?' They did nothing wrong. I really mean this, take the pledge. Visit itsonus.org."
Check out PEOPLE's full Academy Awards 2016 coverage and complete winners list!
"Til It Happens to You" – co-written by Gaga and Diane Warren – was recorded for The Hunting Ground, a documentary about rape on college campuses.
Biden applauded Gaga's performance on Twitter writing, "Proud to stand by my friend @LadyGaga tonight. Pure courage that inspires, challenges us all. #ItsOnUs. All of us."
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Following the powerful Oscars segment, celebrities stood behind the It's On Us campaign on social media.
Kesha, Kerry Washington, Jessica Chastain, Matt McGorry and Mariska Hargitay were just some of the A-listers who tweeted in support.
.@kesharose I'll be thinking of u 2nite. This is not over we'll stand by u until you are free to live a HAPPY life. Everyone deserves that.— Lady Gaga (@ladygaga) February 28, 2016
In the front row at the Dolby Theatre, Brie Larson was spotted hugging all the survivors from Gaga's performance as they exited the stage.