The 23-man matchday squad contains seven new Lions and the starting XV does not include any of the players that began the 59-8 win over the Barbarians in Hong Kong last weekend.
O'Driscoll's first game for the Lions came in the 116-10 win over a Western Australian XV in Perth on June 8, 2001, when he started at full back. He scored the last of his side's 18 tries that day and will be making his first appearance of his fourth tour on his return to Perth this week.
Five of the starting team, Manu Tuilagi - who partners O'Driscoll in midfield - Sean O'Brien, Ian Evans, Dan Cole and Rory Best, will be making their Lions debuts, while six of the starting side are backing up having played off the bench against the Barbarians.
Ireland veteran O'Driscoll is joined in the starting XV by seven of his countrymen, with Tommy Bowe picked on the right wing, Jonathan Sexton and Conor Murray combining at halfback, Cian Healy and Best packing down in the front row and O'Brien and Jamie Heaslip named at openside flanker and No8 respectively.
Leigh Halfpenny and George North complete the backline at full back and left wing, while debutant Dan Cole starts at tight-head prop, with Ospreys duo Ian Evans and Alun Wyn Jones chosen in the second row and Tom Croft included on the blindside flank.
There are two debutants among the replacements in the form of Leicester pair Ben Youngs and Geoff Parling, while Mako Vunipola, Toby Faletau, Owen Farrell and Sean Maitland are all selected having started against the Baa-Baas.
Front rowers Tom Youngs and Matt Stevens complete the matchday 23 having both been on the bench in Hong Kong.
"The lads who played in Hong Kong put down a marker as they performed extremely well in very tough conditions. I am sure that this team playing against the Western Force will be just as eager to show their mettle in Perth," said Lions Tour manager Andy Irvine.
"I told the team in Hong Kong that they were custodians of the red jersey. That responsibility is now with this group of players and I am confident they will give their all against the Force. This is the first match of the tour in Australia and the Lions are keen to make a winning start here."
British & Irish Lions (v Western Force, June 5, Patersons Stadium, 1800/1100 BST time)
15. Leigh Halfpenny (Cardiff Blues/Wales)
14. Tommy Bowe (Ulster/Ireland)
13. Brian O'Driscoll (Leinster/Ireland, captain)
12. Manu Tuilagi (Leicester Tigers/England)
11. George North (Scarlets/Wales)
10. Jonathan Sexton (Leinster/Ireland)
9. Conor Murray (Munster/Ireland)
1. Cian Healy (Leinster/Ireland)
2. Rory Best (Ulster/Ireland)
3. Dan Cole (Leicester Tigers/England)
4. Alun Wyn Jones (Ospreys/Wales)
5. Ian Evans (Ospreys/Wales)
6. Tom Croft (Leicester Tigers/England)
7. Sean O'Brien (Leinster/Ireland)
8. Jamie Heaslip (Leinster/Ireland)
16. Tom Youngs (Leicester Tigers/England)
17. Mako Vunipola (Saracens/England)
18. Matt Stevens (Saracens/England)
19. Geoff Parling (Leicester Tigers/England)
20. Toby Faletau (Dragons/Wales)
21. Ben Youngs (Leicester Tigers/England)
22. Owen Farrell (Saracens/England)
23. Sean Maitland (Glasgow Warriors/Scotland)