Federer, who won the tournament in 2009, was unable to find a foothold in the match as Wawrinka powered his way to a 6-4 6-3 7-6 (7/4) victory.
It means Federer has failed to reach the last four in three consecutive years at Roland Garros while Wawrinka will now face either Kei Nishikori or Jo-Wilfried Tsonga for a place in the final.
“I’m already thinking what I’m going to do over the next few days, because Wimbledon is going to be a big goal for the season,” said the seven-time Wimbledon champion.
“That’s where I want to play my best. It’s a big goal for me. I want to win it, and I feel like my game is good.
“It’s been solid, it’s been positive, and I have just got to keep it up now.”
Wawrinka will now face local favourite Jo-Wilfried Tsonga, who pulled off a stirring fightback to beat Japanese fifth seed Kei Nishikori 6-1 6-4 4-6 3-6 6-3.
Tsonga, who often suffers lapses in concentration, lost his momentum following a 40-minute suspension in play after a side panel from the scoreboard fell on the crowd from the upper part of Court Philippe Chatrier, injuring three fans.
Tsonga is seeking to become the first Frenchman to win his home slam since Yannick Noah in 1983.
In the women’s tournament, Ana Ivanovic and Lucie Safarova will meet in the French Open semi-finals after both players came through their last-eight matches in straight sets.
Ivanovic beat Ukraine’s Elina Svitolina 6-3 6-2 while Safarova, who knocked out Maria Sharapova in the previous round, defeated Spain’s Garbine Muguruza 7-6 (7/3) 6-3.
The triumph was particularly sweet for Ivanovic, who has not been past the fourth round at Roland Garros since being crowned champion seven years ago.
The 27-year-old was a deserving victor, hitting 37 winners to Svitolina’s eight and sealing a comfortable win in one hour and 15 minutes.
“I’m very, very thrilled to be in the first semi-finals since 2008,” Ivanovic said. “It’s been a long road and hard work.”
The other two women’s quarter-finals take place today with top seed Serena Williams taking on Italian Sara Errani and Belgium’s Alison van Uytvanck up against Swiss Timea Bacsinszky.
In the men’s Andy Murray will face Spain’s David Ferrer today for a place in the semi-finals.
2pm: (1) Serena Williams (USA) v (17) Sara Errani (Ita), (1) Novak Djokovic (Ser) v (6) Rafael Nadal (Spa) Suzanne Lenglen: 2pm: (23) Timea Bacsinszky (Swi) v Alison Van Uytvanck (Bel), (3) Andy Murray (Gbr) v (7) David Ferrer (Spa) Court 1: (1) Martina Hingis (Swi) & Sania Mirza (Ind) v (7) Bethanie Mattek-Sands (USA) & Lucie Safarova (Cze), (4) Su-Wei Hsieh (Tpe) & Flavia Pennetta (Ita) v (9) Andrea Hlavackova (Cze) & Lucie Hradecka (Cze), Katarina Srebotnik (Slo) & Horia Tecau (Rom) v (2) Bethanie Mattek-Sands (USA) & Michael Bryan (USA), Jie Zheng (Chn) & Henri Kontinen (Fin) v Lucie Hradecka (Cze) & Marcin Matkowski (Pol).