The Citizens have never won UEFA's prize competition, but with the addition of Erling Haaland, they will feel this is their year.
City have dominated the Premier League since Pep Guardiola's arrival, but they have yet to translate that form to Europe.
Meanwhile, Sevilla haven't beaten an English side in the Champions League group stages since 2007 and have only won one of their last eight in this competition.
Julen Lopetegui's side has also been decimated by sales over the summer transfer window, with the likes of Jules Kounde and Diego Carlos departing.
Therefore, this will be a tough test for Sevilla and they must find a way to keep Haaland quiet, considering he has scored ten goals in his first seven games for City.
The Champions League is always a special competition and Man City are one of the favourites to go on and lift the trophy this time and a win in Spain would be the perfect start.
Sevilla v Manchester City: talkSPORT commentary
This Champions League clash is set to take place on Tuesday, September 6.
Kick-off at the Ramon Sanchez-Pizjuan Stadium is at 8pm UK time.
Coverage will start at 7pm with Adrian Durham and in addition to this game, talkSPORT will also have live updates from Celtic v Real Madrid, PSG v Juventus and the Lionesses against Luxembourg's Women in their World Cup qualifier.
Commentary from Man City's game will come from Jim Proudfoot and Danny Mills, while talkSPORT.com will also have a live blog of the action.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream. You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
Sevilla v Manchester City: Team news
Kyle Walker limped off in the closing stages of City's 1-1 draw with Aston Villa and appears unlikely to be involved tomorrow.
Aymeric Laporte is still on the sidelines for the defending Premier League champions, while Nathan Ake and Jack Grealish returned to the bench after short spells out.
Sergio Gomez and Manuel Akanji could make their debuts for City on Tuesday after signing from Anderlecht and Borussia Dortmund.
Haaland played the full 90 minutes at Villa Park, so it remains to be seen if he is in the starting XI.
Kalvin Phillips could also be available after overcoming a shoulder problem.
Sevilla meanwhile are expected to be without Marcao, Karim Rekik and Jesus Corona.
Former Manchester United man Adnan Januzaj lacks match fitness, while Kasper Dolberg could start after joining from Nice on deadline day.
Manchester City v Sevilla: What has been said?
Man City goalkeeper Ederson: "We all work to achieve that goal of winning it. We know the grandeur of the competition and the level of the teams involved.
"If they are involved in the competition, it's because they are the best teams in Europe. The reality is that only one team can win.
"It's a trophy that we all want to win."
Manchester City v Sevilla: Match facts
This will be the second season in which Sevilla and Manchester City meet in major European competition; the only previous instance saw the Citizens win home and away in the 2015-16 UEFA Champions League group stage.
Sevilla have won just one of eight group stage games against English Premier League sides in the UEFA Champions League (D3 L4), beating Arsenal 3-1 in November 2007.
Manchester City have won just three of their 13 away games at Spanish opponents in major European competitions (D2 L8), although one of those was at Sevilla in November 2015 (3-1).
Sevilla have qualified for the UEFA Champions League for a third successive campaign; they are unbeaten on MD1 in each of their last six appearances in the competition (W2 D4), although each of their last four openers have been drawn, including twice against English sides (2-2 v Liverpool in 2017-18, 0-0 v Chelsea in 2020-21).
Manchester City are competing in the Champions League for a 12th season - all coming in a row since 2011-12. Only Real Madrid (26), Barcelona (19) and Bayern Munich (15) are on longer ongoing runs of consecutive appearances in the competition (including 2022-23). The Citizens have progressed from their group in each of their last nine seasons in the tournament.
Manchester City lost two of their three away games in last season's UEFA Champions League group stage (W1); they had only lost one of their previous 13 away group games in the competition before this (W8 D4).
Sevilla have won just one of their last eight UEFA Champions League matches (D4 L3), and could suffer back-to-back defeats in the competition for the first time since November 2015, a run of four losses that included two against Man City.
This will be Man City manager Pep Guardiola's first meeting with Sevilla since March 2012 in LaLiga as Barcelona boss, goals from Xavi and Lionel Messi securing him a 2-0 win. Guardiola has won just one of his last seven UEFA Champions League away games against Spanish sides (D1 L5), a 2-1 win at Real Madrid with Man City in February 2020.
Ivan Rakitic has been directly involved in four of Sevilla's last six UEFA Champions League goals (two goals, two assists). The Croatian last season became the club's oldest ever scorer in the competition, at the age of 33 years and 203 days when he netted against Wolfsburg.
Manchester City striker Erling Haaland has scored 23 goals in 19 UEFA Champions League appearances, the best goals/game ratio of any player in the competition's history (1.2 - min. 10 apps). The Norwegian scored eight goals in six appearances for Salzburg and 15 in 13 for Borussia Dortmund, with four of his goals coming in two matches against Sevilla in 2020-21.