The 35-year-old, who now hopes to end his international career by lifting the trophy in Paris on Saturday, marked his world-record 140th Test cap by deftly setting up tries for Johnny Sexton and Andrew Trimble.
Cian Healy, Sexton again, Sean Cronin, Fergus McFadden and Jack McGrath also touched down in a one-sided contest, but the occasion was all about O'Driscoll, who received a rousing standing ovation when he was substituted after 61 minutes. The centre fought back tears as he admitted he was still getting used to the prospect of retirement.
"I haven't let myself think about. It's emotional," said O'Driscoll, who also set a Six Nations appearance record of 64. "It's been a huge part of my whole adult life and to leave here it's going to be hard. But it's a good way to leave today and hopefully we set ourselves up for next week.
"I feel humbled by the reaction. It seems a bit of a joke that you get man of the match for 60 minutes. But I've loved my time playing in this jersey. It had to come to an end at some stage and I'm glad I'm able to go out at home with a big win. It will only properly set in when I've had a bit of time."
On the match against France he added: "Hopefully next week there's a performance and a championship in this team. We have to go there with huge positivity. It's one thing playing in this jersey, but it's another thing altogether winning in this jersey, and we've built a good standard. We're capable of doing great things and we have to start next week by trying to win a second championship as this unit of players."
Chants of "one more year" rang around the ground at the final whistle, but O'Driscoll's summer retirement is not in doubt. However, while the legs may no longer be willing, the brain remains tack-sharp. Classic mis-direction has long been where O'Driscoll's magic has lain and he treated his adoring crowd to one final delve into his repertoire.
Ireland spent 20 phases huffing and puffing around the fringes from the off, only to stroll through the door straight from a centre-field scrum. O'Driscoll's shallow run to the gain-line and his blind pass invited Sexton into the run-around, and the gleeful fly-half ghosted through the gap and under the posts.
Italy were neither overawed or overwhelmed, immediately forcing themselves on to the front foot, and a huge chunk of fortune, in the shape of a slice off O'Driscoll's boot, brought them back on level terms.
After Trimble's thunderous midfield tackle dislodged the ball, O'Driscoll tried to boot in behind the defence, only to flick possession straight to Leonardo Sarto. Italy's left wing raced down his flank, wrong-footing first Rob and then Dave Kearney, and cantered under the posts. Luciano Orquera's conversion made the score 7-7, with Ireland stunned.
However, Joe Schmidt's men kept their cool, and further pressure eventually told when Sexton slotted a penalty to reclaim the lead.
Eoin Reddan, on in place of the unwell Conor Murray, scampered close to Italy's whitewash with a sharp scrum-base break, but Ireland's control was not restored until Ulster wing Trimble jinked over in the left corner, just ahead of half time.
Again it was master schemer O'Driscoll with the telling act as he exploited to perfect reward the fact centre partner Gordon D'Arcy had to receive treatment on the field.
Cutting blind from static play in the Italy 22, O'Driscoll dodged D'Arcy, the physio and referee Nigel Owens before finding Trimble in the half-yard required for Ireland's second try. Italy scrum-half Tito Tebaldi was penalised for throttling Ireland captain Paul O'Connell off the ball after the restart.
Sexton rejected a shot at goal to punt the penalty to the corner for an attacking line-out. Ireland set the maul from the line-out, only for Italy to blunt the drive and clear to touch. The Irish pack came again from another well-worked maul, though.
Reddan sniped close to the line and prop Healy drove home for Ireland's third try. Sexton grabbed his second and Ireland's fourth, taking the scoring pass from Dave Kearney after O'Driscoll's crucial pass over the top of the defence.
After the departure of O'Driscoll, which was followed by Paddy Jackson replacing Sexton, presumably with Paris in mind, hooker Cronin bundled over for his first international score.
McFadden then bisected the defence for Ireland's sixth score, as the hosts cranked up their points-difference dominance in the Six Nations standings.
Replacement prop McGrath bolstered those figures further with the seventh and final try on the stroke of full-time as the life of Brian, for Ireland in Dublin at least, drew to a glorious close.