The Germans, meanwhile, reached the semi-final last season and will be looking to stamp their authority with a win here given that they will have to finish ahead of at least one of Paris Saint-Germain or Manchester United in order to progress from Group H.
Leipzig have made a fantastic start to the Bundesliga season, sitting in first place after four matches with three wins and a draw keeping Julian Nagelsmann's side unbeaten.
Goals from Angelino and Yussuf Poulsen were enough to secure a comfortable 2-0 win at Augsburg on Saturday as they continue to adjust to life without Timo Werner following the striker's £45m move to Chelsea in the summer transfer window.
Having conceded only two goals so far in the domestic campaign, Nagelsmann appears to be running a tighter ship than in his debut season at the club. Dayot Upamecano certainly stood out with his commanding performances in August's Champions League knockout rounds, with the central defender reportedly being tracked by several of Europe's traditional elite clubs.
For now, though, the France international remains a Leipzig defender and his side's hopes will heavily hinge on him keeping that defensive back three organised and tough to score against.
After winning the Turkish Super Lig for the first time in their history last season, Istanbul Basaksehir have made a disastrous start to defending their title this season.
Saturday's 2-0 win at Trabzonspor was their first win of the season, a record which is currently keeping them in the relegation zone after three defeats and a draw prior to the weekend's desperately-needed victory.
The 35-year-old was the club's joint-top goalscorer with 13 league goals last season alongside Bosnian winger Edin Visca, who did at least get himself off the mark at the weekend.
Other familiar faces at the side, who were only formed in 1990, include former Manchester United full-back Rafael Da Silva, ex-Liverpool defender Martin Skrtel and former Tottenham winger Nacer Chadli.
RB Leipzig form (all competitions): WWDWW
Istanbul Basaksehir form (all competitions): LLLDW
Otherwise the 33-year-old looks to have a clean bill of health to choose from and may even find himself tempted to rest a few players given Leipzig's opponents' lack of form.
Any complacency would certainly help lift a Turkish outfit desperately lacking in confidence, though. While it may be the club's first ever Champions League group-stage match, that is not the case for many of their players, which should help them compete in the early stages.
However, quality and energy does look to be an issue, especially with Chadli doubtful to take part. Muhammed Sengezer has been ruled out with a shoulder injury, with Azubuike Okechukwu and Hasan Ali Kaldirim unlikely to feature due to knocks.
RB Leipzig possible starting lineup:
Gulasci; Kolstermann, Upamecano, Halstenberg; Mukiele, Sabitzer, Kampl, Angelino; Olmo, Forsberg; Poulsen
Istanbul Basaksehir possible starting lineup:
Gunok; Caicara, Skrtel, Epureanu, Bolingoli; Visca, Tekdemir, Kahveci, Aleksic; Ba, Crivelli
We say: RB Leipzig 3-0 Istanbul Basaksehir
Providing Nagelsmann opts to go close to full-strength in terms of his starting XI, this should be a comfortable victory for Leipzig.
The German side will be buoyed by their surprising progression to last season's semi-final in this competition and simply look as if they have far more quality and energy than an ageing Istanbul Basaksehir side in terrible recent form.