Totti, 38, defied his age with a sublime finish to cancel out Sergio Aguero’s early penalty for City at the Etihad Stadium.
It was little more than the in-form Serie A side deserved for a high-quality display of attacking football.
Again City goalkeeper Joe Hart, returning to the side after sitting out the club’s two previous matches, was kept busy.
Former City defender Maicon, who conceded the third-minute penalty, hit the bar and Miralem Pjanic spurned three good chances as Roma attacked in the way the hosts might have hoped to do.
City had some good moments, with David Silva and Frank Lampard threatening in the second half, but again their European progress looks like being far from straightforward.
The result left them third in the group and already trailing leaders Bayern Munich by five points.
City did look sharp in a high-energy start and Maicon, returning to the ground where he played out an undistinguished 2012-13 season, looked sluggish as he pulled Aguero back in the area.
Referee Bjorn Kuipers was slow to blow his whistle as he waited for a signal from one of his assistants, and Maicon complained vigorously when he did, but the decision was correct.
Aguero made no mistake from the spot but City were unable to build on their early advantage as Roma responded superbly.
The Italians were first to most loose balls and slick in possession, hitting City with a series of attacks.
Maicon almost made immediate amends for his blunder as he latched onto a lofted Totti pass and smashed a fierce shot against the woodwork.
The veteran Brazilian went through on goal again moments later but was flagged offside.
Gervinho also showed pace that Arsenal supporters saw all too infrequently for their liking when he burst through and was met by a brave Hart.
Hart was again in action as Radja Nainggolan shot straight at him from distance.
City felt they were denied another penalty when Aguero collided with Kostas Manolas and they were caught napping as Totti struck his sublime equaliser after 23 minutes.
The veteran was afforded huge space as he latched onto a Nainggolan pass and he took full advantage as he closed in on Hart and then flicked a deft shot over the goalkeeper.
The landmark goal meant Totti, who celebrated his latest birthday last weekend, had eclipsed Ryan Giggs as the oldest goalscorer since the European Cup was rebranded as the Champions League. It was also his first strike in England.
Roma then threatened to take the lead with their next attack but Cole was flagged offside as he stretched to reach a cross.
It seemed City were getting outplayed at their own game but Edin Dzeko had a chance when he shot weakly at goal.
City had another penalty appeal turned down when Jesus Navas’ low cross struck the hand of the sliding Manolas and Vincent Kompany’s follow-up shot flew over.
Gervinho again showed great pace to get behind City’s sluggish back line but Hart beat away his shot.
Roma maintained their pace after the break, with Totti driving across goal and Pjanic shooting at Hart before curling another effort wide.
City roused themselves as substitute James Milner drove wide and Fernandinho almost got into a shooting position before on-loan Newcastle player Mapou Yanga-Mbiwa barged him away.
Pjanic had another good chance from the edge of the area after another quick Roma attack down the left but again he missed the target.
City sent on Lampard for Dzeko just before the hour and he showed his goal threat with a long-range shot that Lukasz Skorupski tipped away. Silva also showed good control outside the box but poked a long-range effort wide.
Totti was given a good hand by all sides of the ground as he made way for fresh legs after 72 minutes.
City did finish strongly in his absence but Silva flicked a good chance wide - and was offside anyway - and substitute Stevan Jovetic twice drove over.