Vickery, who will be involved in his fourth match on the tour, took over as captain on the field for a brief period when O'Driscoll was replaced against the Golden Lions, but the former England skipper will have the honour from the start for the first time on this his second Lions tour.
Vickery's London Wasps team mater Riki Flutey gets his first start on tour after proving his fitness with a brief second half appearance in the midweek win over the Sharks.
"The coaching staff is very pleased with the way the squad reacted to some bad injury news this week. The players took the news on the chin, trained well, focussed on the next match and the performance against the Sharks was excellent," said Lions head coach Ian McGeechan.
"The squad is very close as a group of players but now there is now a competitive edge developing as we approach the Test series. That is how it should be."
McGeecahn has told all the players that places in the side for next week's first Test are still up for grabs.
"I reminded the players when I told them the team to play Western Province that we were not selecting the Test side until next Tuesday following the Southern Kings match," added McGeechan.
"The team for Western Province will be captained by Phil Vickery who is one of the many leaders in the squad. It is just reward for a thoroughly professional player who will play in his 10th Lions match. Vicks is a former captain of England and he played three Lions Tests against Australian in 2001.
"No starting players are backing up from the Sharks match as we continue our desire to see all players involved in at least two full matches prior to Test selection. Martyn Williams comes into the starting XV following his recovery from a shoulder knock and Riki Flutey gets his first starting role after proving his fitness off the bench against the Sharks."
Lions tour manager Gerald Davies said he was delighted his team had remained unbeaten over the first four games of the tour and is looking to extend that run into next week's Castle Series.
"As a tour party we are delighted that we have reached Cape Town and the final Saturday provincial match prior to the Test series with an unbeaten record. Team morale is high and each team that takes the field is determined to maintain the momentum and to fight for an individual Test place."
British & Irish Lions (vs Western Province)
15. Rob Kearney (Leinster/Ireland)
14. Tommy Bowe (Ospreys/Ireland)
13. Keith Earls (Munster/Ireland)
12. Riki Flutey (London Wasps/England)
11. Ugo Monye (Harlequins/England)
10. Stephen Jones (Scarlets/Wales)
9. Harry Ellis (Leicester Tigers/England)
8. Andy Powell (Cardiff Blues/Wales)
7. Martyn Williams (Cardiff Blues/Wales)
6. Joe Worsley (London Wasps/England)
5. Nathan Hines (Perpignan/Scotland)
4. Donncha O'Callaghan (Munster/Ireland)
3. Phil Vickery (London Wasps/England, captain)
2. Matthew Rees (Scarlets/Wales)
1. Andrew Sheridan (Sale Sharks/England)
16. Ross Ford (Edinburgh/Scotland)
17. Euan Murray (Northampton Saints/Scotland)
18. Simon Shaw (London Wasps/England)
19. Tom Croft (Leicester Tigers/England)
20. Mike Blair (Edinburgh/Scotland)
21. James Hook (Ospreys/Wales)
22. Gordon D'Arcy (Leinster/Ireland)