Among the sides taking to the field over the next two days are two former champions and four debutants, while three countries will be represented in the competition for the very first time.
1. Al Hilal have a point to prove
Since Al Ittihad defended their AFC Champions League title in 2005, no other side has been able to retain the trophy – indeed, Urawa Red Diamonds' run to the 2008 semi-finals (when they entered at the quarter-final stage as holders) was as close as anyone has managed.
However, 2019 champions Al Hilal went into last year's edition as many people's tip for the title, boasting a formidable squad replete with Saudi internationals and foreign superstars, among them the likes of the previous year's top scorer and MVP Bafetimbi Gomis, Andre Carrillo and Salem Al Dawsari.
But disaster then struck in the most unfortunate of circumstances. Having won their opening three games, a COVID-19 outbreak within their squad meant the defending champions were unable to field a team for their Matchday Four encounter against Pakhtakor and were subsequently forced to withdraw. Ulsan Hyundai went on to win the title and the rest is history.
The Saudi Pro League champions, though, may well still consider themselves as the best club side in Asia, and they will be desperate to regain their throne to make up for the misfortune of 2020. With a starting XI largely unchanged from the past couple of years – albeit under new manager Rogerio Micale – they begin their Group A campaign at home to AGMK on Thursday with a point to prove.
2. A huge moment for Indian football
A founding member of the Asian Football Confederation, India has been represented by its club sides in continental competitions for more than five decades, with prestigious teams including Mohun Bagan, East Bengal and, more recently, Bengaluru FC all making a name for themselves in AFC tournaments.
However, since Asian club football moved into its new era towards the beginning of the millennium, it has been the AFC Cup in which the aforementioned sides have shone. The AFC Champions League's expansion, though, now means for the very first time there will be an Indian side in the group stage.
As the 2019-20 Indian Super League champions, FC Goa will not only make their AFC Champions League bow, but will also make their first-ever appearance in a continental competition. And they will do so as Group E hosts at Pandit Jawaharlal Nehru Stadium in Margao, kicking off against Qatar's Al Rayyan on Wednesday.
Formed just seven years ago, the Gaurs are the newest side in the West Zone, but Goa is among several hotbeds of football across India. While their passionate fans may not be able to attend, there is sure to be plenty buzz around their competition debut as they get set to embark on an historic adventure.
3. Air Force Club make long-awaited return
Between 2004 and 2008, Iraqi giants Air Force Club appeared in the AFC Champions League group stage on three occasions, but when it comes to continental club football it has been the AFC Cup in which they have made their name.
Such was their dominance in that tournament that the Baghdad side won an unprecedented three successive titles between 2016 and 2018. Indeed, in three campaigns they suffered just two defeats, and it is a competition which they have never failed to win when entered.
Given their record across that period, they may have considered themselves unfortunate that when Iraqi sides returned to the AFC Champions League group stage in 2019 it was domestic champions Al Zawraa, and not Air Force Club, who gained direct entry into the competition as the AFC Cup champions fell at the play-off round.
But, after a penalty shootout victory over Saudi Arabia's Al Wehda last week, Air Force Club finally get to make their long-awaited return. Still featuring many of the stars from that 'three-peat' – including captain Hammadi Ahmed, striker Amjad Radhi and the returning Humam Tareq – it will be intriguing to see how they handle they step up as they begin their Group B campaign against Sharjah on Wednesday.
4. How will the other three debutants fare?
In addition to the aforementioned FC Goa, three more teams will make their AFC Champions League bow in the coming days, with Uzbekistan's AGMK and Tajikistan's FC Istiklol lining up in Group A and Jordan's Al Wehdat among the contenders in Group D.
Uzbekistan has been represented in the tournament since the first edition in 2003, but AGMK have only risen to the fore in recent years. Having advanced passed Al Gharafa last week they face a daunting opening to the competition against Al Hilal. But, under former national team head coach Mirdjalal Kasimov, who previously guided Bunyodkor to the semi-finals, there could be plenty of room for optimism.
Twice runners-up in the AFC Cup, meanwhile, FC Istiklol will become Tajikistan's first-ever representatives in the group stage. The Dushanbe side almost caused a major upset in the 2020 playoffs when they ran Al Ahli Saudi close in Jeddah, and they return to Saudi Arabia once more, opening their Group A campaign against the UAE's Shabab Al Ahli Dubai on Thursday.
Finally, Al Wehdat are one of Jordan's famous old clubs and over the years have been a major feature in the AFC Cup, where they have made the semi-finals and Zonal semi-finals on a number of occasions. Having previously suffered defeats in the AFC Champions League qualifying rounds, the Amman side move to the big stage, starting against Saudi powerhouse Al Nassr on Wednesday.
As the trio prepare to create new chapters in their respective histories, all eyes will be on with how they handle the step up.
5. Al Sadd
Since the 2018 AFC Champions League, Al Sadd have been back among the major players in the competition, twice reaching the semi-finals only to suffer narrow defeats. Then, in what they would surely consider a disappointing showing, falling to Persepolis in the 2020 Round of 16 when many had considered them title contenders.
The Doha side return to the group stage for the fourth successive year, and they do so off the back of an incredible year domestically as they regained the Qatar Stars League from Al Duhail, storming to the title with an unbeaten campaign during which they drew just three of 22 matches.
Since being eliminated by Persepolis last September, the only losses Xavi Hernandez's side have suffered have been in the Qatari Stars Cup, and they go into their tournament opener against Foolad Khouzestan in Riyadh having yet to taste defeat in 2021.
It all points to Xavi, who stepped into the role in mid-2019, having found his feet as a head coach. The 2011 champions boast a side brimming with quality – including 2018 top scorer Baghdad Bounedjah, 2019 AFC Player of the Year Akram Afif and Spanish wizard Santi Cazorla – and will likely start the tournament as one of the highly fancied teams.