Gokhan Inler and Edinson Cavani both grabbed a brace each with Marek Hamsik also on target as Walter Mazzarri's side tore Pescara to shreds.
Birkir Bjarnason had given the visitors hope when he reduced the arrears in the first half, but a red card to Antonio Bocchetti capped a day to forget for Cristiano Bergodi's men in Naples.
In response to Juve's 3-0 win over Torino on Saturday night, Napoli were straight onto the attack in the lunchtime kick-off with Hamsik testing Mattia Perin early on.
Inler gave Napoli the lead in the 10th minute as he jinked past Romulo Togni before sending in a powerful shot which Perin was unable to reach.
Five minutes later Hamsik made it two, pouncing on the ball after former Pescara striker Lorenzo Insigne's effort was blocked, and dispatching it past Perin.
Pescara showed their first signs of life three minutes later with Bjarnason scoring his first goal in Serie A with a header.
Cavani was then denied by Perin as Napoli looked to restore their two-goal advantage.
Not only did they do that in the 58th minute, but they were given a man advantage after Bocchetti was sent off for denying a goalscoring opportunity by fouling Cavani inside the box, and the Uruguayan striker made no mistake from the spot.
Cavani put the result beyond doubt in the 63rd minute with a shot which cannoned in off the underside of the crossbar.
Inler added a fifth in the 78th minute with a shot from distance as Napoli comfortably moved back to within two points of Juve.