Lopetegui, who was ousted as Spain manager on the Eve of the World Cup, will be eager to seize the chance to get his hands on the first piece of silverware as Los Blancos begin life without Zinedine Zidane and Cristiano Ronaldo.
While pre-season results have been largely positive, Lopetegui could hardly have been handed a tougher start in his first competitive outing as they take on their fierce city rivals.
If Real are to win a third consecutive Super Cup, and a record-equalling fifth overall, they must get the better of an Atletico side who have proven a match for their neighbours in the years since Diego Simeone became the coach.
“My first official game is a final. A match that Real Madrid have earned the right to play in once again,” Lopetegui told his new club’s official website.
Of Atletico he added: “They’re a team we know well and it’ll be a local derby. It’s all set up to be a great match and a great final.”
Atletico have themselves won twice before in this annual meeting of the European champions and Europa League winners, and they come here to the Estonian capital fresh from beating Marseille 3-0 in the Europa League final in May.
Wednesday’s game could come too soon for Luka Modric, with the Croatian playmaker only just back from a post-World Cup holiday. Meanwhile, new signings Thibaut Courtois and Alvaro Odriozola have travelled.
For Atleti, it has been a rather more serene couple of months, especially with star striker Antoine Griezmann opting to reject a move to Barcelona and stay at the club.
Griezmann and defender Lucas Hernandez are only just back after helping France to World Cup glory, while new signings include their compatriot Thomas Lemar, Croatian striker Nikola Kalinic and Portuguese star Gelson Martins.
Simeone is aiming for his seventh trophy as Atletico coach, although he will have to watch the game from the stands as he serves a touchline ban.
“We need to improve on what we did last season. Expectations are high,” said Simeone, who is hoping to set the tone for a campaign that will culminate with the Champions League final being played in their own stadium.