An injury to Wyn Jones has opened the door for Sutherland who was originally named among the replacements for the match in Cape Town.
England’s Mako Vunipola comes into the matchday 23 to provide loosehead cover on the bench.
Jones sustained a minor shoulder injury in training but the Lions are hopeful he will be available for the second Test next weekend.
“It’s really bad luck for Wyn and we all feel for him missing out on tonight’s game,” said Warren Gatland, the Lions head coach.
“However, we’re confident he’ll be back in training next week and have no plans to bring in anyone else at this stage.”
Sutherland’s inclusion means there are four Scotland internationals in a Lions starting Test XV for the first time in 28 years.
The Hawick prop joins Stuart Hogg, Duhan van der Merwe and Ali Price in the side to take on the Springboks.
The last time four Scots started was in the first Test in 1993 in New Zealand when Gavin Hastings captained a side which included Kenny Milne, Paul Burnell and Andy Reed. The All Blacks won the game in Christchurch 20-18.
Revised British & Irish Lions team (v South Africa, Cape Town Stadium, Saturday, 5pm BST)
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. Rory Sutherland (Worcester Warriors, Scotland)
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. Mako Vunipola (Saracens, England)
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)