European skipper Thomas Bjorn has selected just one of his four wildcard picks, Paul Casey, for the first session, with the 41-year-old taking on Jordan Spieth and Justin Thomas alongside his fellow Englishman Tyrrell Hatton.
Rory McIlroy will take Danish rookie Thorbjorn Olesen under his wing in the second match of the day against world number one Dustin Johnson and Rickie Fowler.
But 14-time major champion Tiger Woods will draw much of the attention as he plays his first Ryder Cup since 2012 in the fourth match to hit the Albatros course at 0655 GMT.
The 42-year-old will renew his rivalry with Molinari, after the two faced off in the singles at both the 2010 and 2012 events, before the Italian won the British Open in July while playing alongside Woods, who had led with eight holes to go.
Woods will have ‘Captain America’ Reed for company, and the Masters champion lived up to his moniker by responding to jeers at Thursday’s opening ceremony at Le Golf National by cupping his ear.
But world number 12 Fleetwood said he won’t be daunted by the duo on his Ryder Cup debut.
“In my first Ryder Cup match, I couldn’t pick a better player (Molinari) to play with,” he told Sky Sports.
“It’s a massive match, of course everyone is talking about Tiger’s return, but we’ve just got to focus on our game.”
— Ryder Cup USA (@RyderCupUSA) September 27, 2018
Although the Americans have assembled a side featuring nine major champions, Europe also have one of their strongest-ever outfits, with Rose and Rahm looking like a potentially formidable pairing.
Koepka, who has won three times in his last six appearances at major tournaments, could have to shoulder the responsibility of hitting his team’s first tee shot in front of an intimidating 6,900-capacity grandstand.
“I think it’s a very good opportunity to kind of get a great start,” he said. “You know, you want to do it against their two best players, and that’s kind of how we’d love to do it.”
World number two Rose won the $10 million FedEx Cup prize last Sunday, while Rahm will be hoping to continue a proud tradition of Spanish heroes in the Ryder Cup, after the feats of Seve Ballesteros, Jose Maria Olazabal and Sergio Garcia in the past.
“We’re going to figure out a way to win the match,” Rose told Sky Sports.
Despite a relatively poor Ryder Cup record, with just two wins from 11 matches, Fowler is bullish about his chances with Johnson against four-time major champion McIlroy and Olesen.
“I feel like (I’m) getting matched up against Rory in a lot of the team matches, I’ve played against him plenty,” said the 29-year-old, who is playing in his fourth Ryder Cup.
“I’m confident in my partner going head-to-head with those guys… It’s going to be a hard-fought match.”
Good friends Spieth and Thomas will be strong favourites against Casey and Hatton.
“Doesn’t matter who you’re playing. We have to play good golf,” said Thomas.
Both captains have named four pairings that have been previously untested in Ryder Cups, with Bjorn notably choosing to blood four of his five rookies at the first opportunity.
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© Agence France-Presse (Additional edits from Richard Barrett)