Edin Dzeko on Sunday got the hosts off to the perfect start in the clash between two of Italy's heavy hitters with frenetic, end-to-end attacking encounter.
Inter eventually equalised midway through the second half thanks to Ever Banega's close-range finish but within minutes Roma were back ahead, as Manolas met Alessandro Florenzi's free-kick as a subsequent deflection off the attending defender took it past visiting goalkeeper Samir Handanovic.
Luciano Spalletti's side preserved their advantage this time, seeing out the game for a win that puts them third in the table after seven games with 13 points -- five behind league leaders Juventus. Lazio, Chievo and Milan are fourth, fifth and sixth, respectively.
Milan came back from 1-3 down to defeat Sassuolo in Milan. Carlos Bacca, Manuel Locatelli and Gabriel Paletta led the comebacks for the home team.
In Rome, it proved to be a thrilling contest at the Stadio Olimpico, with an especially breathless first half that saw plenty of chances at either end. Dzeko scored after just five minutes, turning home Bruno Peres' low cross after good work from Mohamed Salah but that was only the start of the drama.
Both sides had plenty of chances -- Banega smashed a 25-yard drive against the post, before Salah tested Handanovic twice with one-on-one scoring opportunities but a second goal proved maddeningly elusive.
The visitors perhaps spent more time on the ball but it was Spalletti's side which had the greater attacking threat, and this continued into the second half. Yet it was Inter who would eventually get the all-important equaliser: Banega received Mauro Icardi's flick before turning inside Daniel De Rossi and sliding home.
Roma could have been discouraged by that blow -- instead they responded almost immediately. A free-kick wide on the right -- won by Peres offered Florenzi the chance to curl one into the box, and his delivery was met by a stooping Manolas right around the penalty spot.
The header might have been on target anyway, but an almost immediate deflection off his marker ensured Handanovic had no chance of stopping it as the Olimpico celebrated wildly.
The Inter goalkeeper, who was impressive all evening, had one last great intervention to make, clawing away Dzeko's header that would have clinched things three minutes from time.
That gave Inter a final chance to push forward in search of a second equaliser but the hosts held firm to clinch a valuable win and go into the international break with renewed confidence.
"We played well tonight, we started strongly and had lots of chances besides the goal," Roma's veteran midfielder De Rossi said. "We afforded them some opportunities but we were more solid than usual.
"We dropped too deep in the second half but our response to their equaliser was incredible. That shows the team is getting back to its old self, once and for all."
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