Foals have said they are "honoured and thrilled" to be announced as a headline act for Latitude 2022.
The festival will take place at Henham Park, Suffolk, from 21 to 24 July.
Lewis Capaldi, Snow Patrol, Maggie Rogers, Little Simz and Manic Street Preachers will also perform.
Latitude's organiser said it was "famed for cultivating artists" and Foals' set was expected to be one of the "many unforgettable experiences of the weekend".
Foals said: "It's especially significant to us as our first ever festival headline set was at Latitude almost ten years ago and we remember the rush of that show like it's today.
"It felt like being handed the controls to a jumbo jet at 35,000 feet. Latitude helped us and many other great UK bands realise their potential.
"We couldn't be happier to come back on the Saturday night to remind everyone and ourselves how powerful and euphoric live music can be."
Double Brit Award winner Lewis Capaldi will make his debut at the Suffolk festival after he pulled out of the 2021 event.
Last July's festival went ahead as a government test event with headliners that included Wolf Alice, The Chemical Brothers, Bastille, and Bombay Bicycle Club.
It had a daily capacity of 40,000 and following the event up to 20 people in Suffolk tested positive for Covid-19, the county's director of public health said.
Snow Patrol are expected to return after they headlined the inaugural Latitude in 2006. Due to illness they cancelled their headline slot in 2019 and a guest slot in 2021 due to Covid.
The Northern Irish band said: "We are so delighted to be back playing Latitude once again. It's one of the best festivals in the UK and we can't wait."
Russell Howard said he "can't wait" to take the headline slot on the Comedy Arena stage. He will be joined by poet and comedian Tim Key, comedian, writer, actor and broadcaster Rosie Jones and Taskmaster's Alex Horne, who will perform with his musical comedy act The Horne Section.
Bessie Turner will perform on the BBC Sounds stage, as will fellow Suffolk act Gaffa Tape Sandy.
Organiser Festival Republic says influencer Anchal Seda will talk about her new book What Would the Aunties Say? which addresses "taboo topics" within South Asian culture, including "careers, colourism, relationships and mental health".