Roma needed two late goals from Adem Ljajic to deny plucky Sassuolo an historic victory in the Serie A match at the Stadio Olimpico.
The Giallorossi rested talismanic captain Francesco Totti with Wednesday's crucial Champions League showdown with Manchester City in mind and the capital club missed his leadership as Sassuolo snaffled two early goals in Saturday's 2-2 draw.
Simone Zaza scored both, first capitalising on Morgan de Sanctis' goalkeeping gaffe and then beating the Roma stopper from a close encounter only minutes later.
Daniele De Rossi's dismissal shortly after the break spelled doom for Roma but they rallied to cut the deficit through a Ljajic penalty 12 minutes from time.
As the seconds ticked away, the Serbian rifled a last-gasp leveller before Sassuolo defender Sime Vrsaljko saw red to rub salt in the visitors' wounds.
All the early signs were positive for Roma, who welcomed Kevin Strootman back into the starting XI for the first time since he suffered a season-ending injury in March.
The Dutchman's attempt to convert Mapou Yanga-Mbiwa's cross was blocked by Matteo Brighi before Paolo Cannavaro cleared Miralem Pjanic's free-kick to safety.
It came as a huge surprise, then, as Sassuolo opened the scoring in the 15th minute.
De Sanctis was almost entirely to blame as he dawdled on Yanga-Mbiwa's backpass to allow Zaza to saunter over and hook the ball into the unguarded net.
Further embarrassment was to come as the Italy striker managed to double up only three minutes later.
This time the Roma back-line was at fault, with poor positioning allowing Zaza to collect a long-ball from Simone Missiroli and round the stranded De Sanctis from a one-on-one.
It was the first time Roma, who had previously only shipped two goals in the capital this season, had conceded twice at home in the league since February 2013.
They fought back and Pjanic was unlucky to miss the mark with a swipe at Ljajic's free-kick. The latter then saw his powerful drive repelled by Andrea Consigli before Juan Iturbe slammed the ball over the crossbar.
Jose Holebas soon clattered the beam with a ripping effort, but the last chance of the half belonged to Sassuolo.
Back in his defensive role, Greece international Holebas did remarkably well to anticipate Domenico Berardi's finish when it had looked rather easy for him to turn home Federico Peluso's low cross.
If Roma had resolved to make amends after the restart they had not clued in midfielder De Rossi, whose foul on Berardi in the 50th minute earned him his second yellow card and left his team a man light.
De Sanctis would, however, find a grain of personal redemption as he denied Berardi with a remarkable one-handed save shortly before the hour.
Totti's absence from proceedings was confirmed when Seydou Keita became Roma's third and final substitute, with the former Barcelona midfielder's introduction signalling the start of a late fightback.
The Giallorossi were given a chance to halve the deficit when Vrsaljko handled Gervinho's shot and Ljajic made no mistake from the penalty spot.
Keita was only denied a clean shot at goal by a great tackle from Cannavaro and, when Francesco Acerbi cleared the ball off Ljajic in the 90th minute, it looked like Sassuolo had done enough.
But after Gervinho's pinpoint pass helped Alessandro Florenzi beat the offside trap, all that remained was for the Italian to feed Ljajic for an easy equaliser off his right boot.
Sassuolo subsequently lost Vrsaljko as the Croatian picked up his second yellow card of the game, but the northerners could at least take solace from the fact they had forced a famous draw in the Eternal City.