The iconic centre and former captain is set to bow out on Saturday as the Irish take on France in Paris for the chance to be crowned Six Nations champions.
O'Driscoll, whose career has spanned 15 years, will make his world-record 141st and final international appearance in the crucial game at the Stade de France.
It follows last weekend's emotional farewell in Dublin, during which the 35-year-old gave a man-of-the-match performance as Ireland beat Italy to keep their Six Nations hopes alive.
The playmaker told a packed Aviva Stadium: "There's a championship in this team. We need to go to France with huge positivity and try and relive what happened in 2000."
Ireland head into the weekend as strong favourites with only a win required, unless England win well against Italy in Rome earlier in the day.
Ulster's Paddy Jackson looks set to miss out on the decider with boss Joe Schmidt favouring the versatility of Leinster fly-half Ian Madigan.
Jackson's club teammates Andrew Trimble, Rory Best and Chris Henry all start the game while Iain Henderson drops to the bench for the Stade de France showdown.
Ian Madigan is in line for his first appearance of the season in Saturday's crunch fixture.
Madigan will provide cover from the bench for Johnny Sexton, on Brian O'Driscoll's 141st and final Test appearance for Ireland.
Fit-again Peter O'Mahony is the sole change to the starting line-up from the 46-7 hammering of Italy in Dublin last weekend.
Madigan could find himself thrust into Ireland's highest-pressure Six Nations situation since their 2009 Grand Slam decider against Wales in Cardiff, if he joins the fray.
The 24-year-old has only 11 Leinster starts to his name this term too, sharing duties with Kiwi playmaker Jimmy Gopperth.
Now head coach Joe Schmidt has backed the Leinster out-half to shoulder a hefty burden, as Ireland chase just their third win in 42 years in Paris.
Ian is a very good player and he does give us coverage through the midfield and at full-back.
Conor Murray and Cian Healy have both overcome niggling problems to retain their starting berths.
Scrum-half Murray's illness forced him out of the Azzurri rout in the first quarter, but Munster's British Lion had made a full recovery.
Wrecking ball loosehead prop Healy trudged out of the final stages in Dublin last weekend after picking up an ankle strain.
The 26-year-old Leinster front-rower spent Saturday night with his foot in a compression boot, and the precautionary measure paid dividends with Healy back to full training as early as Tuesday.
O'Driscoll will extend his Six Nations appearance record to 65 in his final international before his summer retirement.
The 35-year-old Leinster stalwart and Gordon D'Arcy will extend their world-record international centre partnership to 56 joint appearances.
Ireland boss Joe Schmidt backed Madigan to handle the pressure in Paris if called into action.
"Sometimes you make those replacements because of injury and sometimes to change up what you're doing," Schmidt said.
"I feel confident Ian's the right man to do those two things for us within the current squad.
"He played through the autumn and he has trained with us for the full eight weeks throughout this tournament.
"If you can't show confidence in a player then perhaps you've got to go outside the squad, and that's not ideal either.
"It's been a pretty combative campaign - we just started to creak a little bit, so we just needed the coverage."
He added: "In England we got a couple of niggles, and we didn't have as broad a coverage on the bench as we would have liked.
"If Johnny had been injured, Paddy would have started.
"But it's Ian's ability to cover 10, centre and 15.
"He's a reasonably confident young man. He's a massively hard-working young man as well.
"We're in a really luxurious position. It was always a concern when Ronan O'Gara retired, but then Johnny replaced him.
"And now we've got two emerging 10s behind him growing into the role."