Not since Diego Maradona inspired them to domestic titles in the 1986-87 and 1989-90 seasons have the Partenopei come close to challenging for the Scudetto, but Wednesday night's victory ensured they are guaranteed to finish behind Juventus.
Influential midfielder Marek Hamsik broke the deadlock eight minutes after the interval, star man Edinson Cavani added a penalty just after the hour before Swiss midfielder Blerim Dzemaili ensured there was no way back for Bologna, who dominated the first half.
The hosts dominated the first half, with on-loan Genoa forward Alberto Gilardino shooting over from distance, as did Rossoblu captain Alessandro Diamanti - who then forced Napoli goalkeeper Morgan De Sanctis into action with a decent effort from just outside the box.
The pressure continued to build as Diamanti found an opening into the area but he was once again denied by a fine stop from De Sanctis.
In first-half injury time, Gilardino should have done better with a close range header that just missed the target.
Perhaps stung into action over their woeful showing over the course of the half by boss Walter Mazzarri, who declared their loss at Bologna last season as "where we lost the chance to qualify for the Champions League", the Azzurri responded positively.
Cavani had already blazed over before Hamsik opened the scoring, picking up the ball on the edge of the box and unleashed a stunning left-foot shot that left inexperienced 19-year-old Bologna goalkeeper Dejan Stojanovic with no chance.
Bologna's failure to capitalise on their first half dominance was further compounded 10 minutes later, Cavani netting from the spot after being fouled by Stojanovic in the area.
There was no way back for the hosts when Cavani teed up Dzemaili to tap into an empty net in the 67th minute.
Christian Maggio thought he had bagged a fourth when he was allowed to slot home but the 31-year-old Italy international was flagged offside.
It mattered little, however, as Napoli cruised in the final minutes to seal victory which put them seven points ahead of third-placed AC Milan with two matches remaining.