Lionel Messi will be back in a Barcelona shirt in La Liga, while Inter Milan begin their bid to end Juventus' grip on the Serie A title and potential challengers face off in Germany and France.
AFP Sport picks out some of the standout action in Europe this weekend:
Lionel Messi is staying at Barcelona for at least one more year and on Sunday he will be the centre of attention as the Catalans belatedly kick off their campaign in La Liga.
The game, behind closed doors, against Unai Emery's Villarreal is also new coach Ronald Koeman's first competitive outing in charge after one of the most turbulent summers in Barcelona's history.
While Messi stayed against his will, Luis Suarez has departed for Atletico Madrid, following Ivan Rakitic, Arturo Vidal and Nelson Semedo out of the door. Miralem Pjanic and the Portuguese international Trincao have come in.
Barcelona are a team in transition but there is no doubt that, as long as Messi is still there, anything is possible.
"Barca are a great side. I'm pleased that Messi has stayed and that we will continue to enjoy having him in La Liga," said Emery, whose own team has already played twice, winning one and drawing one.
Antonio Conte's Inter get their Serie A campaign underway against Fiorentina at San Siro having been given the opening weekend off due to their run to the Europa League final last month.
The Nerazzurri lost that game to Sevilla and also finished a point behind Juventus in the Serie A title race, so now their aim is to end the Turin side's long domination of Italian football.
With Juve having beaten Sampdoria 3-0 in Andrea Pirlo's first game as a coach, Inter need to get off to a good start and there will be plenty of focus on the new arrivals: Vidal but also Achraf Hakimi, the Moroccan full-back signed from Real Madrid for 40 million euros ($44.9m) after impressing on loan at Borussia Dortmund.
The Bundesliga is a hugely entertaining league but once again there are doubts as to whether any team can seriously threaten Bayern Munich's hegemony.
Dortmund are the most likely contenders, while it remains to be seen if Leverkusen or Leipzig can mount a real challenge this time.
Leipzig finished third last season and reached the Champions League semi-finals. Leverkusen were fifth, just behind Borussia Moenchengladbach.
Julian Nagelsmann's Leipzig remain the last team to hold Bayern while Peter Bosz's Leverkusen are the last side to beat the Bavarians in Munich. But both teams lost their star player over the summer, with Leipzig's Timo Werner and Leverkusen's Kai Havertz moving to Chelsea.
So can they successfully replace them and compete again?
Leipzig this week paid Crystal Palace 20 million euros ($23m) for Alexander Sorloth, who is a direct Werner replacement. Meanwhile, Leverkusen recently signed Czech forward Patrik Schick from Roma. He was on loan at Leipzig last season.
Nagelsmann's side were 3-1 winners against Mainz on the opening weekend but Leverkusen were held 0-0 at Wolfsburg. Saturday's clash, before a limited crowd, will provide a measure of where both sides currently stand.
While Paris Saint-Germain have endured a slow start to their French title defence having been handicapped by a coronavirus outbreak, suspensions and injuries, there is a fresh look for now at the top of Ligue 1.
Saint-Etienne and Rennes are level on points at the summit and they meet on Saturday amid hope that this campaign does not simply turn into another PSG procession.
Nobody realistically believes Saint-Etienne can add to their record tally of 10 titles though, even if manager Claude Puel is so far enjoying some success after overhauling his squad and promoting youth.
Rennes are a more interesting case, and not just because in 17-year-old midfielder Eduardo Camavinga they have possibly the hottest young property in world football.
The Brittany side finished third in the last, curtailed season and have been busy investing ahead of a first appearance in the Champions League. They have just sold goalkeeper Edouard Mendy to Chelsea, but they are certainly going to be worth watching this season.