Bundesliga history is set to be made Friday as two Americans face off as head coaches for the first time in Germany's top flight when Jesse Marsch's RB Leipzig host Pellegrino Matarazzo's VfB Stuttgart.

"I hope it's a big deal in America," Leipzig coach Marsch said Wednesday.

"It was unimaginable a few years ago that two American coaches could play against each other in a top league.

"I have so much respect for 'Rino' (Matarazzo) and his history. We have a big challenge coming up on Friday."

Stuttgart thrashed promoted Guerther Fuerth 5-1 last Saturday on the opening weekend of the season.

In contrast, last season's runners-up RB Leipzig slipped to a shock 1-0 defeat at Mainz, despite the hosts having 11 squad members quarantined after three players tested positive for Covid-19.

Marsch, who hails from Wisconsin, wants his side to play with "more clarity" after struggling to break down Mainz's deep-sitting defence.

After winning consecutive Austrian league and cup titles with Red Bull Salzburg, Marsch, 47, joined their sister club RB Leipzig this season to replace Julian Nagelsmann, who is now at Bayern Munich.

Matarazzo, a New Jersey born Italian-American who has spent the last 20 years playing and coaching in Germany, took charge of Stuttgart in 2019.

Before that, he was Nagelsmann's assistant coach at Hoffenheim in 2018/19, when Marsch had a similar role on RB Leipzig's coaching staff.

Marsch is looking forward to seeing Matarazzo again, more than two decades after the pair played football against each other while studying in America.

"Yeah, so 'Rino' and I have a little bit of history," said Marsch.

"We played against each other at university in the US.

"He's pretty much German at this point even though his name is completely Italian.

"His German is really good, he's done a very good job with Stuttgart.

"He's worked his way up through academies and really earned it the hard way.

"And as an American, I'm very proud of the success he has had."