The duo will represent Team Europe against Jack Sock and Frances Tiafoe of Team World at the O2 Arena in London.
At 19:00 BST, Andy Murray will play Alex de Minaur in the first singles match in the evening session.
The 20-time Grand Slam champion Federer said last week that he would call it quits during the team tournament, which gets underway on Friday.
The 36-year-old Spaniard Nadal, who has 22 major wins, would be “amazing” to play with, according to the 41-year-old Swiss.
Federer stated, “I’m not sure whether I can take it all, but I’ll try.”
“This one has a really distinct feeling. Being on his squad and not competing against him makes me pleased.”
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Against the American pair, Nadal said he was anticipating an “unforgettable” showdown with his foe.
The Spaniard said, “one of the most significant, if not the most important player in my tennis career is departing.”
“In the end, this situation will be challenging. But, I’m ecstatic and appreciative to play with him.”
Federer has suffered from a knee issue and cannot compete in singles matches.
In the Wimbledon quarterfinals of the previous year, Hubert Hurkacz defeated him in his most recent encounter.
Italian Matteo Berrettini will replace Federer over the weekend in the three-day Laver Cup, which pits Europe against a team from around the globe.
Casper Ruud of Norway will play Sock on Friday during the day session, while Stefanos Tsitsipas of Greece will play Diego Schwartzman of Argentina.
Novak Djokovic, a 21-time Grand Slam champion, is a member of Team Europe under Bjorn Bjorg’s leadership.
Team World, which also features Canadian Felix Auger-Aliassime and Americans Taylor Fritz, is coached by John McEnroe.
Federer created the Rod Laver Cup, with 10 singles matches and two doubles sets. Europe has won all four prior iterations of the competition.
On Friday, Saturday, and Sunday, each victory in a game is awarded one point, two points, and three points, respectively. The first team to accumulate 13 points is deemed the champion.