The team features six changes to the starting line-up from the side that lost 16-15 to the Wallabies in Melbourne last Saturday, which levelled the three-match series following the Lions' 23-21 victory in the Brisbane opener.
Irish centre O'Driscoll, expected by many to take the captaincy after Sam Warburton suffered a tour-ending hamstring injury, was left out of the matchday squad altogether, bringing a premature end to his 12-year career with the tourists.
The 34-year-old, who was on his fourth Lions tour but still searching for his first Test series win, started both previous Tests but coach Warren Gatland said he thought Welshman Jamie Roberts offered "something more".
"Obviously he was pretty disappointed as anyone is disappointed but he appreciated the fact that he was spoken to before the announcement," Gatland said at the team's base in Noosa, Queensland.
"It's the first time any coach has ever had that decision with him in 15 years of rugby so it's not easy for that to be the first time.
"He's still going to be very important to us in the next 72 hours in terms of his experience and leadership."
Roberts, who missed the first two Tests with a hamstring injury, and Jonathan Davies will instead start in the centres, two of 10 Welshmen in the starting line-up.
Toby Faletau comes in at number eight for Ireland's Jamie Heaslip and Mike Phillips, who played in the first Test but was rested for the second because of concerns about his knee, returns at scrum-half in place of England's Ben Youngs.
Irishman Sean O'Brien replaces Warburton at openside flanker in the new-look back row, which suggests the Lions will again look to blow the Wallabies away up front rather than play too expansively.
Loosehead prop Alex Corbisiero returns in the front row after missing the second Test with a calf problem, pushing his England team-mate Mako Vunipola, who was heavily penalised at the scrum in Melbourne, back to the bench.
Welshman Richard Hibbard gets the nod over England's Tom Youngs at hooker for his first Test start of the tour with his compatriot Adam Jones again providing the fulcrum at tighthead.
Gatland said choosing the team had been difficult and that the "head had ruled over the heart in many selection decisions".
"We've had a few players coming back from injury, and for quite a few positions as well, between the first and second Tests, they were toss-up positions," he added.
"It was quite a lively meeting we had with the coaches last night in terms of making the final selection. It was tough, but we've come up with a side we think is good enough to do the job on Saturday."
The New Zealander said the team had been picked before Wyn Jones, who played in all three Tests on the last Lions tour to South Africa four years ago, was chosen as the best candidate to captain the side.
"Hopefully, it was about the way I play and not about the way I lead. It's as simple as that," said the 27-year-old lock.
"I played first with an eye on getting in the Test selection and to be in the position I am in for the final Test is pretty special for me personally, but there's still a job to do."
With O'Driscoll failing even to make the bench, the power of England's Manu Tuilagi was preferred to cover the backline, while flanker Justin Tipuric and Scottish lock Richie Gray also get a first chance of tasting Test action on the tour.
"It all comes down to Saturday," Gatland added. "Winner takes all. We know we can leave nothing in the tank and that only a complete performance will get us across the line."
Team: 15-Leigh Halfpenny (Wales), 14-Tommy Bowe (Ireland), 13-Jonathan Davies (Wales), 12-Jamie Roberts (Wales), 11-George North (Wales), 10-Jonathan Sexton (Ireland), 9-Mike Phillips (Wales), 8-Toby Faletau (Wales), 7-Sean O'Brien (Ireland), 6-Dan Lydiate (Wales), 5-Geoff Parling (England), 4-Alun Wyn Jones (captain, Wales), 3-Adam Jones (Wales), 2-Richard Hibbard (Wales), 1-Alex Corbisiero (England)
Replacements - 16-Tom Youngs (England), Mako Vunipola (England), 18-Dan Cole (England), 19-Richie Gray (Scotland), 20-Justin Tipuric (Wales), 21-Conor Murray (Ireland), 22-Owen Farrell (England), 23-Manu Tuilagi (England)