Having seen Juventus extend their lead at the top of Serie A to six points with their 2-0 home win over Fiorentina, the game was a must-win match for both sides as they looked to keep their respective Scudetto dreams alive.
Lazio were looking to pick themselves up after successive league defeats but found themselves up against Walter Mazzarri's Partenopei outfit who had won five of their last six.
The Biancocelesti were buoyed by the return of influential Brazilian playmaker Hernanes and he nearly opened the scoring after two minutes when his left-footed strike from the edge of the box bent inches wide of De Sanctis' post.
Stefan Radu was then presented with a decent goalscoring opportunity when he peeled off his marker to flick Antonio Candreva's corner just over the crossbar before Candreva had a penalty appeal rightfully turned down.
However, Lazio were rewarded for their early pressure after just 11 minutes when Sergio Floccari controlled Abdoulay Konko's cross on his chest expertly before volleying home. It was the 31-year-old's fourth league goal of the season.
Candreva twice went close to extending his side's advantage, first watching his thumping free kick parried by De Sanctis before the Napoli shot-stopper finger-tipped his shot across goal around the post.
Lazio were forced into a change midway through the first-half when captain Stefano Mauri suffered a knock and was replaced by Bosnian midfielder Senad Lulic. The substitute made an instant impression, producing a brave header to prevent Edinson Cavani from nodding in Goran Pandev's cross after Marchetti had spilled Juan Zuniga's effort from distance.
Floccari then nearly produced one of the goals of the season when he unleashed a vicious piledriver from nearly 30 yards, but the Lazio talisman was denied a second goal by the inside of the woodwork.
The woodwork was then rattled at the other end minutes later when Cavani rose highest to meet Zuniga's cross with a thumping header which crashed off the underside of the crossbar. The Napoli players appealed that the ball had crossed the line but referee Daniele Orsato rightfully waved play on.
Napoli had De Sanctis to thank as the veteran goalkeeper pulled off a brilliant save to palm away Hernanes' curling free kick moments before the half-time whistle.
Floccari proved a constant thorn in Napoli's side and the striker had the ball in the net four minutes into the second half, bundling home Andre Dias' flick-on from close range, only to be denied by the linesman's flag.
De Sanctis then produced a calamitous error when he misread a deep Lazio clearance but the goalkeeper's blushes were spared as Campagnaro raced back to stop Lulic's lob from sneaking over the goal-line.
Lulic then spurned a glorious opportunity to seal the win when he dispossessed Campagnaro and with just De Sanctis to beat, the Bosnian somehow fired straight at the goalkeeper.
His profligacy was to prove costly as Campagnaro turned hero, acrobatically volleying Hamsik's corner into the top corner in style.
Walter Mazzarri's side nearly stole all three points in the dying embers when former Lazio striker Goran Pandev unleashed a shot from distance, but the Macedonian striker was denied by a smart stop from Marchetti.
In a game of end-to-end drama, Floccari was denied once again by the woodwork in the 92nd minute when his header from Candreva's cross struck the crossbar before Candreva's dipping drive fizzed past the post in what was a remarkable finish to a thrilling contest.
The result means that Napoli remain in second position, five points behind leaders Juventus.