Some 175,000 people were expected to descend on Worthy Farm outside Glastonbury in Somerset, southwest England, in sizzling temperatures but with reinforced security measures after a string of terror attacks in Britain.
"Hooray! Welcome to Glastonbury!" said founder Michael Eavis, greeting those queueing outside as the green metal gates opened.
Shows on the seven biggest stages start on Friday, but rucksack-lugging revellers like to get there early to secure a decent spot to pitch their tents in.
"There were some checks but there are so many people and it is so hot. The queues were better than I thought they would be," said Anna Harris, 25, from south London, who was among the first to get in.
Tickets cost £238 ($300, 270 euros) and all 135,000 have sold out, with a further 40,000 people accredited to attend.
"It's like going to another country, a hip and thrilling Brigadoon that appears every year or so," the festival said.
"You enter a huge tented city, a mini-state under canvas. British law still applies, but the rules of society are a bit different, a little bit freer. Everyone is here to have a wild time in their own way."
Glastonbury started off as a loss-maker in 1970, with 1,500 people paying one pound to watch Marc Bolan top the bill, with free milk from the farm to tempt music-loving hippies.
It is now one of the world's landmark music festivals, with dozens of stages, fields and areas. The site has a perimeter of about 8.5 miles (13.5 kilometres).
Radiohead top the bill Friday on the main Pyramid Stage, backed up by The XX, Royal Blood and Kris Kristofferson.
On Saturday, the Foo Fighters are headlining, after sets by The National, Katy Perry, Run the Jewels and Craig David.
Sheeran closes the festival on Sunday, supported by Biffy Clyro, Chic and Barry Gibb.
Opposition Labour Party leader Jeremy Corbyn is due to give a talk and introduce US rap duo Run The Jewels.
On the secondary Other Stage, Major Lazer, Alt-J and Boy Better Know are the headliners, with sets from Liam Gallagher, Kaiser Chiefs, Emeli Sande and The Courteneers.
Status Quo, Goldfrapp, The Pretenders, The Jacksons, Dizzee Rascal, Alison Moyet and Kiefer Sutherland are also on the bill.
Movie star Johnny Depp will present the 2004 film he starred in, "The Libertine", in a new film zone at the festival.
- 'Pee power' -
Worthy Farm will have 10 information signs powered by urine, thanks to a new 40-person urinal near the Pyramid Stage.
The urine is converted into electricity thanks to technology developed by the University of the West of England.
A second "Pee Power" site at the festival will charge lighting and mobile phones.
Organisers and police have urged attendees to pack light and expect searches.
"The policing style may look and feel slightly different this year," police officer Caroline Peters said.
"Like the rest of the UK, festival-goers should be alert but not alarmed," she said, following four terror attacks in recent months in London and at a Manchester pop concert.
Mobile phone network EE, which is providing free wi-fi on site, is expecting Glastonbury to be the most shared live event of the year, with 40 terabytes of data predicted to be used.
There will be no festival in 2018, with the dairy farm needing a fallow year every five years to recover.