The Italians, shock victors against Wales a week earlier, found the Irish a different proposition altogether, although they managed to breach the Ireland line for the first time in the championship with Denis Dallan's 55th-minute try.
Ireland, though, scored five tries of their own through O'Driscoll - his 18th which took him past Brendan Mullin in the all-time list - Geordan Murphy, John Kelly, Peter Stringer and David Humphreys, who also kicked five goals for a 17-point haul.
Ireland shrugged off the absence of three first-choice backs through injury and the loss of prop Reggie Corrigan with a wrist injury before half-time to secure an eighth successive win stretching back to last June in Auckland.
Italy coach John Kirwan had suggested the only way to stop Ireland and subdue the enormously-talented O'Driscoll was to fix him up with a beautiful woman and ply him with champagne the night before.
The clean-living Irishman had clearly enjoyed a restful night for he was once more in inspiring form, scaring the life out of the Italian defence with each touch of the ball.
The 24-year-old Dubliner produced some sublime handling skills and he finished decisively on 59 minutes, crashing onto Humphreys' well-rehearsed inside ball, to claim the 18th try of his international career.
In a match packed to the brim with Irish heroes, Victor Costello led a magnificent pack performance and helped lay the platform for half-backs Stringer and Humphreys to unleash their side's devastating threequarters.
Stringer clearly enjoyed his much-heralded spat with Alessandro Troncon, the Italian captain who had been sent off in this fixture two years ago for poleaxing the little man from Cork.
Troncon had raised the pre-match tempo by accusing his opponent of provocation but Stringer let his rugby - and his pinpoint passing in particular - do the talking.
He also scored only his second try in 30 games for Ireland when pouncing at the base of a strong drive from his forwards on 18 minutes.