The song got particularly emotional for Grande during a verse about her parents.
It was a fun dance and a good song, but the moment that will stick in everyone's head comes when Grande trips on one of her vertiginous heels and interrupts herself for a quick "Ohmygod!".
Grande - who had posted on her Instagram Stories earlier this week that she was watching the film - took inspiration from the final, iconic scene, which sees stars Diane Keaton, Bette Midler and Goldie Hawn, resplendent in white suits, belting out Lesley Gore's anthem to self-empowerment, You Don't Own Me.
She helped organize the One Love Manchester concert a year ago, raising more than US$23 million for victims of the Manchester bombing.
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On Tuesday night, she was happy to claim a piece of Tennessee history for women in the Senate. She fought for Tennessee values in the legislature and in Congress.
She moved into more emotional territory as the song progressed, holding back tears while singing about her future wedding day.
However others felt they could relate to her visual depiction of anxiety, including shots of a cloud encompassing her head, Ariana walking in slow motion through a fast-moving room, and then walking through a frozen room.
"I thought we were supposed to exit", Grande says, apologizing for the mishap.
The host reassured her that it was fine. "We support you", host Ellen DeGeneres said after the song. Her performance was pre-taped on November 6, but instead of changing a thing, she embraced her fall with a sense of humor and let her fans see the original take in all of its imperfect glory.
For a closer look into Ariana's "Thank U, Next" lyrics, watch below.