Each club plays eight games - against two opponents from each pot in UEFA's recent draw - and the first round takes place on a special opening matchday, stretched over three evenings.
A total of 18 matches will take place across the continent - from Amsterdam to Zagreb, and several places in between - but some fixtures certainly catch the eye more than others.
Here, Sports Mole assesses the standout contests that could light up stadia and TV screens alike on matchday one.
Tuesday, September 17
JUVENTUS vs. PSV EINDHOVEN
After one year away from Europe's top table, Juventus will welcome Dutch champions PSV Eindhoven to Turin for the clubs' first-ever competitive meeting.
The Bianconeri were banned from European competition last term, due to financial misdemeanours, but they finished third in Serie A and claimed the Coppa Italia before head coach Max Allegri stormed off into the sunset.
Now making their 24th appearance in the Champions League, a rejuvenated Juve side led by ex-Bologna boss Thiago Motta started the season with successive 3-0 wins, and even after two goalless draws either side of the international break, they seem set to challenge for honours.
While Juventus watched on from a distance, PSV made it all the way to the last 16 last season, before going out to eventual finalists Borussia Dortmund.
The Eindhoven club will arrive in Italy full of confidence following a superb 2024 so far, having claimed their first league title in six years with a new national-record points haul, then returned to action with five straight wins, averaging four goals a game in the process.
AC MILAN vs. LIVERPOOL
After several European campaigns under Jurgen Klopp, Liverpool's first under Arne Slot kicks off in illustrious surroundings, as the Premier League giants visit San Siro.
Having twice met Milan in finals this century, the Reds reunite with their Rossoneri rivals, who are also under new management after their own title-winning boss departed during the summer.
Klopp's final hope of more continental glory was extinguished in Bergamo last season, when Liverpool lost to Atalanta BC in the Europa League quarter-finals, and Slot's side will now travel to nearby Milan with a point to prove.
After winning each of their first three league matches without conceding a goal - heralding talk of a title challenge in some quarters - the Merseyside club slumped to a 1-0 home loss against Nottingham Forest last time out.
It has been far from a bed of roses at San Siro since Paulo Fonseca took over from former Scudetto winner Stefano Pioli, but his team did swat aside Venezia at the weekend, after star men Theo Hernandez and Rafael Leao were recalled to the lineup.
Liverpool's 2005 'Miracle of Istanbul' was avenged by Carlo Ancelotti and co in the 2007 Champions League final, but after Milan lost both group-stage meetings three years ago they will want to start off with a home win.
REAL MADRID vs. STUTTGART
There are slight 'mammoths versus minnows' vibes to this intriguing contest at the Bernabeu, which will host the first-ever meeting between these two sides.
The holders now begin their quest for title number 16, just three months after beating another German club in the final to claim a sixth crown in only 10 years.
After adding Kylian Mbappe to their star-studded lineup, Los Blancos have made a sharp start this season, lifting the UEFA Super Cup and going unbeaten through five games in La Liga - albeit they remain four points behind arch-rivals Barcelona in the standings.
As Stuttgart must yet meet Juventus, Paris Saint-Germain and Atalanta during their first Champions League campaign for 15 years - and first attempt at any European competition since 2013 - they would surely have wished for a softer start to their schedule.
Nonetheless, last term's Bundesliga runners-up beat Borussia Monchengladbach at the weekend to record their first league win of the season, raising slim hopes of causing an upset in the Spanish capital.
Wednesday, September 18
MANCHESTER CITY vs. INTER MILAN
Like Liverpool one day earlier, Manchester City will perhaps draw upon memories from Istanbul during their Champions League opener, as they come face to face with their victims in the 2023 final.
The last time City met Inter it was when they secured the treble, and after falling in the quarter-finals last season, Pep Guardiola's men will be keen to go all the way to Munich next May.
The English champions come into this contest in top form, having won their first five matches of the new season - beating city rivals Manchester United in the Community Shield before picking up maximum points in the Premier League.
City lead by two points already, but ahead of a crucial clash with second-placed Arsenal on Sunday, they must first tackle their Italian counterparts.
Reigning Serie A champions Inter have not made a flawless start to their Scudetto defence, but they have won two and drawn two so far - a late goal from Denzel Dumfries saved their blushes in Sunday's stalemate with nearby Monza.
Simone Inzaghi's side - who claimed the Nerazzurri's 20th domestic title last term - also face a seismic few days, as they have half an eye on this weekend's Milan derby.
PARIS SAINT-GERMAIN vs. GIRONA
What could be more romantic than a starry-eyed newcomer making their Champions League debut in the 'City of Light'?
Girona will arrive in Paris following a groundbreaking 2023-24 season that saw them challenge the established powers in La Liga before finishing third in the final standings.
Beating Barcelona and Atletico Madrid along the way, Michel's men proved incredibly tough to beat, and the Catalan club certainly made a major impact in just their fourth top-flight campaign to date.
While Girona are playing their very first European fixture, PSG were runners-up in 2020 and are making their 13th successive appearance in Europe's top club competition.
An expensively-assembled squad have reached the knockout rounds in every season from 2012 onwards, and they have scored in their last 50 Champions League group-stage matches - a run which stretches back nearly nine years.
Luis Enrique's side have lost only one Ligue 1 game in 2024 so far, and having surged back to the top with four wins from four this term, his Mbappe-less squad are already in peak form. Girona beware.
Thursday, September 19
Feyenoord vs. Bayer Leverkusen
With a record of just one defeat throughout an incredible 2023-24 campaign, Leverkusen drew attention from all over the globe for their relentless performances - both in the Bundesliga and on the European scene.
Die Werkself's sole reverse came in the Europa League final against Atalanta, but they had already sprinted clear of Bayern Munich to claim a first-ever league title and later added the DFB-Pokal.
Having shaken off the cruel tag of 'Never-kusen', Xabi Alonso's side now aim to be serial winners, but will second-season syndrome cause their downfall?
Now making only a third Champions League appearance in eight seasons, the German champions must meet last term's Eredivisie runners-up in their opener, which is set to take place in a tinderbox atmosphere at De Kuip.
Dutch champions for the 16th time in 2023, Feyenoord trailed in behind record-setters PSV last May, even though their final total of 84 points was actually two more than when they finished first 12 months earlier.
The Rotterdam club did claim the KNVB Beker as consolation for losing their crown, but beloved boss Arne Slot departed for Liverpool and Brian Priske was brought in to succeed him. So far, things have not run smoothly, with just one win from four league games.
ATALANTA BC vs. ARSENAL
What better way to celebrate completing the renovation of your stadium than welcoming one of England's top clubs for a Champions League contest?
Atalanta will be backed by a full house in Bergamo, as they return to UEFA's elite competition after memorably collecting their first European trophy in Dublin.
Toppling Leverkusen with help from an Ademola Lookman hat-trick, La Dea made up for losing the Coppa Italia final a few days earlier and long-serving coach Gian Piero Gasperini finally got his reward for several years of fine work.
While 'Gasp' will be without key players Gianluca Scamacca and Giorgio Scalvini due to long-term injuries, Arsenal's Mikel Arteta has some short-term concerns - most notably, missing captain Martin Odegaard.
Nonetheless, under Arteta, the Gunners are a significant force once more, and in addition to successive second-place finishes in the Premier League, they made it through to the Champions League quarter-finals for the first time in 14 years.
After putting together 19 appearances in a row under legendary manager Arsene Wenger, Arsenal will try to continue their Champions League rebirth this year: following up victory in Sunday's North London derby with a win in Lombardy is therefore the target.