Starting against Hellas Verona at the Stadio Bentegodi, Paulo Fonseca's side no there will be no easing into the new season - with champions Juventus the visitors to the Stadio Olimpico on the second weekend too.
Here are a few notable elements to have arisen from Wednesday's draw.
Serie A will start on September 19 - the last time the season started so late in the year was back in 2000-01, when the first game took place on September 30. That season, of course, Roma ended up winning the title.
Roma are unbeaten in their last eight opening games of the Serie A season, winning five of those and drawing the other three. The last defeat on the opening day came back in 2011, at home to Cagliari. Last season, meanwhile, the Giallorossi drew 3-3 with Genoa - in what was Paulo Fonseca's first game in charge.
Roma have scored in each of their last nine games to start a Serie A season, scoring an average of 1.9 goals per game. The team have also kept five clean sheets during that period.
Roma and Lazio will play each other on Matchday 18 of the 2020-21 season - something that has only happened once before in the league's history. That was back in 2014-15, in a famous derby that finished 2-2. The game is famous, of course, for the second half brace scored by Francesco Totti - who brought his side back from 2-0 down, and celebrated his dramatic equaliser with a selfie under the Curva Sud.
The second derby of that season also passed into legend: Mapou Yanga-Mbiwa scoring five minutes from the end to beat the Biancocelesti and secure Champions League football for the club.
This season will see the sixth time Roma and Verona have faced each other on the first day of the season. History isn't necessarily so kind on the Giallorossi: four draws and just one win in the meetings to date.
Benevento are the visitors to the Olimpico on the fourth weekend of the season, with the Giallorossi looking to extend a run that has seen them win 23 straight games against newly-promoted sides in league matches.
The last time the Giallorossi didn't beat a newly-promoted side was back in August 2016 - when Cagliari came from behind to draw 2-2 in Sardinia.
Roma have only lost once against Juventus in five previously meetings with the Bianconeri on the second day of the Serie A season - winning two and drawing the other two. The last time the fixture fell on the second week of the season it ended in a Roma victory: Edin Dzeko scoring in a 2-1 win at the start of the 2015-16 season.
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