Lipa delivered a glittery, energetic performance featuring firework displays, five different outfits and an ensemble of break dancers and musicians.
The 28-year-old British-Albanian singer told the crowd how it had been a dream for her to sing on Glastonbury's Pyramid stage, where artists such as Paul McCartney, Beyoncé and David Bowie have performed over the festival's more than 50-year history.
"Little me would just be so beside herself right now," she said. "Honestly I couldn't believe it. I feel so grateful."
Born in London to Kosovo Albanian parents, Lipa began covering songs by other pop artists as a teenager and uploading them to YouTube, which led to a record deal in 2014 when she was 18. In 2019, she won two Grammy Awards including Best New Artist.
The sea of humanity at Glastonbury erupted into dance during hits including New Rules and Love Again.
Lipa also brought Australia's Kevin Parker of Tame Impala fame - a collaborator on her latest album - on stage and the duo performed "The Less I Know the Better" together.
She joined Coldplay, R&B singer SZA and country music singer Shania Twain as headliners - a grouping with much more female talent after criticism over last year's male-dominated line-up.
Earlier on Friday, Seventeen made history as the first K-Pop group to appear at Glastonbury.
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