Osimhen crashed in his third goal is as many games in all competitions with 10 minutes remaining of his first start since early September to hand Napoli a win at one of their fiercest rivals.
Luciano Spalletti's side took advantage of Atalanta's 2-0 home defeat to Lazio earlier on Sunday to move further ahead of the pack and become the only unbeaten side left in Italy's top flight.
"Roma gave us a tough time, they're a good team also, but we showed that we are a very big team. For me it's important to get the goals for the team and it's a big three points," said Osimhen to DAZN.
"We have a big solidarity in the team, everyone knows what they have to do at the right time and we just want to keep up this momentum."
Napoli's nearest challengers are now reigning champions AC Milan following their 4-1 thumping of Monza on Saturday.
Roma are seven points back in fifth after a dogged, battling performance at the Stadio Olimpico which lacked in invention and but largely kept a lid on possibly Europe's most exciting team.
"I think we did enough to merit a draw tonight," said coach Jose Mourinho.
"I wanted to win in the same way they won the game. A couple of shots on target and a goal to win it."
Without injured Paulo Dybala, Roma didn't have a single shot on target and were saved from going behind five minutes before the break when referee Massimiliano Irrati overturned his own decision to award Napoli a penalty for a foul Tanguy Ndombele by Roma goalkeeper Rui Patricio.
Eljif Elmas was denied a close-range tap-in on the hour mark by a magnificent Chris Smalling block and from the resulting corner ex-Roma man Juan Jesus slashed wide after being set up perfectly by Osimhen.
Osimhen then dragged a colossal chance wide with just Patricio to beat after a lightning Napoli counter-attack in the 70th minute.
But the 23-year-old rattled in a much more difficult effort 10 minutes later, charging on to Matteo Politano's booted long pass before holding off Smalling and claiming the three points with a rocket of a finish.
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