Nigeria forward Osimhen rolled home the leveller with 15 minutes left of the first leg of their Champions League last 16 tie at the Stadio Diego Armando Maradona, in his first match since returning from the Africa Cup of Nations.
The 25-year-old equalised Robert Lewandowski's 60th-minute opener, which seemed likely to be the decisive goal as Barca were for long periods the better team, with Napoli's first and only shot on target.
"He's a huge player for us," said Napoli skipper Giovanni Di Lorenzo to Amazon Prime Video.
"He's come back with the right attitude. We knew he would though as he's a great player and professional. He'll give us a hand in the matches to come."
Osimhen had last played for Napoli in a 2-0 defeat at Roma just before Christmas, when he was one of two players from his team to be sent off.
His ninth club goal of the season came at a crucial time, not just in the match but in Napoli's campaign as they play under their third manager of the season in Francesco Calzona, their league title defence up in flames.
Calzona had less than 48 hours to prepare for his first match in charge after replacing Walter Mazzarri on Monday night, and Osimhen gave Napoli a chance of progressing despite a disjointed performance by his team.
Napoli head into next month's second leg in the Catalan capital knowing that with Osimhen in the team there is always a chance of a goal regardless of the overall team display.
"It's a good starting point," added Di Lorenzo.
"We know that we need to do more but we've taken a step forward and now we have a chance in the return leg. It's all to play for."
Osimhen saves Napoli
For Barca meanwhile it was the latest misstep of a complicated campaign at the end of which coach Xavi will leave, assuming president Joan Laporta doesn't sack the coach before then.
The away side had the better chances but couldn't put Napoli away and could yet pay for their wastefulness.
"We're a little disappointed with the result because we could have come out with a win," said Ronald Araujo to Movistar.
"Napoli had a lot of the ball in the last 15 minutes but they barely created a chance. The Champions League is like that."
Barca showed why they were pre-match favourites in the opening exchanges, dominating the ball and creating shooting opportunities which dulled an initially raucous crowd.
Teen sensation Lamine Yamal come close to becoming the Champions League's youngest ever scorer when his ninth-minute effort was well-saved by Alex Meret.
In the 23rd minute, the away side twice went close to taking the lead, Lewandowski's flicked finish kept out by Meret who then tipped away Ilkay Gundogan's long-range rocket.
From that point on Napoli's presence in the game grew, but the hosts failed to let off a single effort on goal before the break despite pushing their opponents on back.
Gundogan forced another smart save from Meret shortly after the restart after being put through by Yamal before blasting over another presentable chance.
Barca had the lead their performance deserved on the hour when Lewandowski collected Pedri's pass and drilled a perfect low finish past Meret.
With the away side looking like they would push home their advantage, Osimhen pounced as Inigo Martinez slipped on the edge of the area to level the scores and transform the atmosphere in the stadium.
Andre-Frank Zambo Anguissa and substitute Giovanni Simeone both had efforts off target with the home side's tails up, but it was Barca who went inches away from snatching a late win.
Gundogan's frustrating night in front of goal continued deep into stoppage time as his low effort flew just wide.
