O’Driscoll last captained the Lions in 2005 when he was spear tackled out of contention by the Kiwis and will take over from fellow countryman Paul O’Connell who was in charge of the Lions 59-8 win against the Barbarians on Saturday.
Squad captain Sam Warburton is expected to play his first match against the Reds next weekend.
The line up picked for Wednesday’s clash does not include any players who played in the opening match in an attempt to give everyone on tour a chance to prove their worth.
Wed 5th June: Western Force vs B&I Lions, Pert, KO 00:00 BST (01:00 CAT)
British and Irish Lions: 15 Leigh Halfpenny, 14 Tommy Bowe, 13 Brian O’Driscoll (c), 12 Manu Tuilagi, 11 George North, 10 Jonny Sexton, 9 Conor Murray, 8 Jamie Heaslip; 7 Sean O’Brien, 6 Tom Croft, 5 Ian Evans, 4 Alun Wyn-Jones, 3 Dan Cole, 2 Rory Best, 1 Cian Healey.
Replacements: 16 Tom Youngs, 17 Mako Vunipola, 18 Matt Stevens, 19 Geoff Parling, 20 Toby Faletau, 21 Ben Youngs, 22 Owen Farrell, 23 Sean Maitland.