With Liam Williams deemed fit enough to take his place on the bench, coach Warren Gatland has opted for a traditional 5/3 bench split of forwards and backs meaning there is no place for Ireland's Iain Henderson in the matchday 23.
Gatland has gambled on the fitness of captain Alun-Wyn Jones who dislocated his shoulder in the warm-up game against Japan but made a quicker than expected recovery and leads this side.
He is partnered by Maro Itoje at second-row, while Courtney Lawes wins the battle for the No 6 shirt ahead of Beirne. The England powerhouse is joined by Tom Curry and Conan in the back-row.
In the front-row, Wales looshead Wyn Jones links up with England's Luke Cowan-Dickie and Furlong in a combination that has never played together before.
Likewise, at half-back, Ali Price and Dan Biggar pair up for the first time as Murray joins his 2017 starting half-back partner from the first Test Owen Farrell in reserve.
The selection will come as a major blow to Murray who started all three Tests in New Zealand and was named tour captain when Jones went down before departure.
He was only selected to start one game, against South Africa 'A', and appears to have carried the can for that performance along with England captain Farrell.
Henshaw plays at inside centre with Elliot Daly after their pair linked up last weekend, while Scotland pair Stuart Hogg and Duhan van der Merwe join Anthony Watson in the back-three as leading try scorer Josh Adams misses out entirely.
On the bench, Wales Ken Owens edges out Jamie George for reserve hooker and there's no place for Mako Vunipola as Rory Sutherland and Kyle Sinckler cover the prop positions.
Beirne and Hamish Watson provide second and back-row cover, while Murray, Farrell and Williams cover the backs.
In a statement, Gatland said it was a difficult selection process.
“In my four Tours as a Lions coach, this was by far the hardest Test selection I have been involved in,” he said.
“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 South Africa ‘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 team to face South Africa (Saturday, Cape Town Stadium, 5.0; Sky Sports)
15. Stuart Hogg (Exeter Chiefs, Scotland)
14. Anthony Watson (Bath Rugby, England)
13. Elliot Daly (Saracens, England)
12. Robbie Henshaw (Leinster Rugby, Ireland)
11. Duhan van der Merwe (Worcester Warriors, Scotland)
10. Dan Biggar (Northampton Saints, Wales)
9. Ali Price (Glasgow Warriors, Scotland)
1. Wyn Jones (Scarlets, Wales)
2. Luke Cowan-Dickie (Exeter Chiefs, England)
3. Tadhg Furlong (Leinster Rugby, Ireland)
4. Maro Itoje (Saracens, England)
5. Alun Wyn Jones – captain (Ospreys, Wales)
6. Courtney Lawes (Northampton Saints, England)
7. Tom Curry (Sale Sharks, England)
8. Jack Conan (Leinster Rugby, Ireland)
16. Ken Owens (Scarlets, Wales)
17. Rory Sutherland (Worcester Warriors, Scotland)
18. Kyle Sinckler (Bristol Bears, England)
19. Tadhg Beirne (Munster Rugby, Ireland)
20. Hamish Watson (Edinburgh Rugby, Scotland)
21. Conor Murray (Munster Rugby, Ireland)
22. Owen Farrell (Saracens, England)
23. Liam Williams (Scarlets, Wales)