The Argentina international found the net in the opening 45 minutes before the Spaniard put the match to bed in the closing stages of the encounter
Gonzalo Higuain gifted Rafa Benitez's men the lead early on, with Jose Callejon eventually making it two with just five more minutes to go.
The hosts started the match with attacking intentions and were rewarded for their positive attitude after just three minutes. A deep ball into the box was deflected into the path of Higuain and the Argentine found the net with an acrobatic finish from close range.
Lorenzo Insigne nearly made it two just minutes later, but his effort from the edge of the area went inches wide. The Italy international continued to trouble the Roma defence, though, and tried his luck once more in the 11th minute, only to be denied by Morgan De Sanctis this time around.
Jose Callejon then came close with a cracking shot after a fine dribble, but his powerful attempt came back off the crossbar.
Napoli continued to dominate proceedings at the San Paolo, with Insigne once more threatening in the 27th minute, but his effort went inches wide of the far corner.
Benitez's men never stopped pushing for a second goal and Insigne nearly doubled his side's tally in the closing stages of the half, but the winger's shot only hit the crossbar.
Roma slowly got into the game after the interval and got their first chance of note in the 54th minute. Miralem Pjanic found Alessandro Florenzi with an intelligent pass, but the Italian aimed wide from inside the area.
Florenzi again looked dangerous shortly after when he tried his luck from a narrow angle, but his shot failed to trouble Rafael.
Callejon should have made it two for Napoli halfway through the second half, but the Spaniard's shot lacked power, allowing Radja Nainggolan to clear it off the line.
There was nothing Roma could do about Callejon in the 85th minute, though, with the versatile attacker picking up Higuain's cross before effectively putting the match to bed with a calm finish.
Napoli have climbed to third spot in the table following Saturday's win with 18 points from 10 games. Roma, meanwhile, sit second in Serie A with 22 points from 10 games.