The superstar overcame her nerves about playing the festival at Worthy Farm in Somerset, as she took the the iconic Pyramid Stage to play a stunning, and typically hilarious gig.
Breaking her silence four songs into her performance, she told the crowd of thousands: "This is the best fucking moment of my whole life.
"Glastonbury means the world to me. I've always wanted to do this my whole life - I've just been too scared."
The set saw her belt out some of her most famous hits including 'Hello', 'Someone Like You' and 'Rolling In The Deep', along with tracks from her most recent record-breaking album, '25', including 'When We Were Young' and 'Send My Love (To Your New Lover)'.
At one point, she restarted her rendition of 'River Lea' after getting "a bit out of breath", and subsequently lost her way again. However, she brushed it off in typical Adele fashion, joking: "Perfect time to fuck up a song, Glastonbury headline set, wouldn't you agree?"
She also had fans laughing when she pulled a Brazilian fan up on stage, only to accidentally burp in her face, blaming it on a "dirty burger".
Watch Adele sing 'Someone Like You' at Glastonbury in the video below...
Adele returned to the UK especially for the set, currently being in the middle of her world tour.
Her turn as a headliner also marked the first time she has ever played the main stage, having previously played to a small tent in 2007, as well as being a regular punter at the festival.
"I've been here a lot of times. I've lost myself a lot of times here. I've had some of the best times of my life here on a Saturday night here at Glastonbury," she told the crowd.
"Hopefully you're all drunk and off your faces - my set will go better then."
Friday night saw Muse open this year's event with their electrifying headline set, while Coldplay will bring the whole thing to a close on Sunday as they take to the Pyramid Stage, which will be the fourth time they have topped the bill.
Adele's full set list:
- 'Rumour Has It'
- 'I'll Be Waiting'
- 'One and Only'
- 'Water Under the Bridge'
- 'Hometown Glory'
- 'Don't You Remember'
- 'Send My Love (To Your New Lover)'
- 'River Lea'
- 'Rolling in the Deep'
- 'Make You Feel My Love'
- 'Set Fire to the Rain'
- 'When We Were Young'
- 'Someone Like You'
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