Robbie Henshaw, Tadhg Furlong and Jack Conan will start for the British & Irish Lions against South Africa at Cape Town Stadium on Saturday.
Tadhg Beirne and Conor Murray have been named as replacements.
Tour captain Alun Wyn Jones will skipper the Lions having recovered from a dislocated shoulder sustained in the tourists' 28-10 win over Japan at Murrayfield Stadium just 24 days ago.
The Welshman will be joined in the second row by Maro Itoje (Saracens, England) who claims his fourth successive Lions Test cap.
Elsewhere, Wyn Jones, Luke Cowan-Dickie and Furlong make up the front row.
Courtney Lawes packs down on the blind side flank to win his third Lions test appearance, having won his previous two from the bench in the second and third Tests in New Zealand in 2017.
Tom Curry is named on the open side, with Conan filling the No 8 shirt.
After impressing against the DHL Stormers last Saturday, scrum-half Ali Price joins out-half Dan Biggar in the half-back berths.
Robbie Henshaw, who made his comeback from a hamstring injury last weekend, partners Elliot Daly in midfield.
Anthony Watson wins his fourth Lions Test cap as he takes his spot on the wing opposite Duhan van der Merwe, with fellow Scot, Stuart Hogg, rounding off the side at full-back.
The starting XV includes three Scots for the first time since the 1997 Tour to South Africa when current Lions assistant coach, Gregor Townsend, was named alongside Alan Tait and Tom Smith for the first and second Tests.
"In my four Tours as a Lions coach, this was by far the hardest Test selection I have been involved in," said head coach Warren Gatland.
"We couldn't have asked for more from the players so far; they’ve all put their hands up and made picking a starting XV incredibly difficult. In truth, we would have been happy with any number of different combinations across the 23, however, we’re very pleased with the side we’ve settled on.
"We know what we’re coming up against on Saturday. It’s going to be an arm wrestle, there’s no doubt about it. We’ll need to front up physically and be ready to go from the first whistle. When we played SA 'A’ last week we probably took a bit too long to get into the game, something we can’t afford to do that again this weekend.
"We need to make sure we play in the right areas of the field, not give them easy territory and take our chances when they come.
"While the stands will be empty in Cape Town Stadium, we know Lions fans from across the home nations will be cheering us on back home. We’ll do our best to get the win."
Lions: Stuart Hogg, Anthony Watson, Elliot Daly, Robbie Henshaw, Duhan van der Merwe, Dan Biggar, Ali Price; Wyn Jones, Luke Cowan-Dickie, Tadhg Furlong, Maro Itoje, Alun Wyn Jones, Courtney Lawes, Tom Curry, Jack Conan
Replacements: Ken Owens, Rory Sutherland, Kyle Sinckler, Tadhg Beirne, Hamish Watson, Conor Murray, Owen Farrell, Liam Williams
Follow South Africa v Lions first Test with our live blog on RTÉ.ie/sport and the RTÉ News app or listen to live commentary with Donal Lenihan and Michael Corcoran on RTÉ's 2fm from 4.45pm Saturday.