Nadal, who turned 33 on Monday, will face 37-year-old Federer for the 39th time.
The Spaniard, chasing a 12th French Open title, leads their head-to-head 23-15 with a 13-2 stranglehold on clay.
That run includes a 5-0 run at Roland Garros — the 2005 semi-final and the 2006, 2007, 2008 and 2011 finals.
“Having Roger in the semi-finals is an extra thing,” admitted defending champion Nadal.
“We shared the most important moments of our careers together on court facing each other.
“So it’s another episode of this, and I’m happy and excited. It will be a special moment, and let’s try to be ready for it.”
Nadal has been in impressive form as he chases an 18th major.
He has dropped just one set so far in making his 12th Roland Garros semi-final and 31st at the majors.
On Tuesday, he demolished Japanese seventh seed Kei Nishikori 6-1, 6-1, 6-3 in his quarter-final.
Nadal has never lost in the semi-finals at the tournament, making Federer’s mission on his return to Roland Garros after a four-year absence look even more daunting.
Not that Nadal is taking anything for granted.
“Roger came back on clay because he’s a player who plays well on all surfaces and on clay he has good chances of winning,” said Nadal who hasn’t lost to the Swiss on clay since the Madrid final in 2009.
“One thing is that he feels physically ready. He’s coming back because he wants to do so. And if he feels in good shape physically, well, he should not leave out a main part of the season.”
Nadal’s record at Roland Garros now stands at 91 wins against just two defeats — to Robin Soderling in the last-16 in 2009 and Novak Djokovic in the 2015 quarter-finals.
A wrist injury forced him to withdraw before the fourth round in 2016.
Many believed those back-to-back setbacks would signal the end of the road for Nadal who has battled a host of injuries throughout his career.
But since that tearful 2016 Paris exit, he has picked up three more majors and twice been a runner-up in Australia.
“After all the problems I have faced, what keeps the flame alive is this desire, the desire to play on the main stages where I’ve been playing tennis for all these years,” he said.
“This won’t last forever. So I want to give myself the maximum chances. For the time being, things are rolling well.”
Results from the 10th day of the French Open on Tuesday (x denotes seeding):
Men
Quarter-finals
Roger Federer (SUI x3) bt Stan Wawrinka (SUI x24) 7-6 (7/4), 4-6, 7-6 (7/5), 6-4
Rafael Nadal (ESP x2) bt Kei Nishikori (JPN x7) 6-1, 6-1, 6-3
Women
Quarter-finals
Johanna Konta (GBR x26) bt Sloane Stephens (USA x7) 6-1, 6-4
Markéta Vondroušová (CZE) bt Petra Martic (CRO x31) 7-6 (7/1), 7-5