Romain Alessandrini and Julien Feret scored two superb first-half goals for Rennes, who had goalkeeper Benoit Costil sent off in the 25th minute and midfielder Jean Makoun dismissed six minutes after the break.
Nene had made it 1-1 for PSG but parity did not last long as they struck the woodwork three times to lose for the second time in two weeks after St Etienne had also clinched three points in the capital.
However, PSG - who were without suspended striker Zlatan Ibrahimovic - stayed top on 23 points after St Etienne wasted a two-goal lead at Evian TG to draw 2-2.
St Etienne are third on 22 points, a point behind second-placed Marseille who are below PSG on goal difference.
Marseille visit Bordeaux, seventh on 21, on Sunday (2000 GMT) while Lyon host Stade Reims (1300).
Valenciennes, who also had top spot within their reach, were held to a 1-1 home draw by 10-man champions Montpellier. They are fourth on 22 points.
Rennes, who have won eight of their last nine games in all competitions, moved up to sixth also on 22 points.
"People will remember it for years because we put on a huge performance tonight," Rennes defender Jean-Armel Kana-Biyik told French channel Canal+.
"Beating PSG here is a remarkable achievement but doing it with nine men is just incredible."
PSG wasted numerous chances as they lacked the sharpness to really trouble Rennes reserve goalkeeper Cheick Tidiane N'Diaye, who produced a great display in his first league game since April 2009.
"We had a lot of chances but we were just not efficient," Nene said.
Rennes started strongly with Alessandrini converting the first clear-cut chance to open the scoring with a splendid half-volley from outside the box on 13 minutes.
PSG, who were unbeaten in the league until St Etienne surprised them, pushed hard for an equaliser.
Nene struck the post from close-range on 18 minutes but his efforts paid off only three minutes later when he clipped the ball over goalkeeper Costil after Javier Pastore had set him up.
Rennes were quickly reduced to 10 with Costil being shown a straight red card for a rough challenge on Jeremy Menez outside the box.
The visitors, however, went back ahead as Feret bent a free kick low into the corner of the net in the 35th minute.
PSG's bad luck continued when the in-form Menez had to be replaced after picking up a thigh problem, while N'Diaye made saves from Blaise Matuidi's volley and Nene's curling effort on the stroke of halftime.
With Makoun's dismissal for a second yellow card six minutes into the second half, PSG poured forward to try to avoid a humiliating defeat.
Substitute Guillaume Hoarau and Pastore went close in the 60th minute but the towering striker was denied by the crossbar and then the playmaker's powerful half-volley hit the post.
At Evian, Max-Alain Gradel's double was not enough to secure his St Etienne side victory.
The Ivorian forward headed home from Pierre-Emerick Aubameyang's neat cross in the ninth minute and then scored into an empty net after Aubameyang's assist to put his side 2-0 ahead at halftime.
Mohamed Rabiu inspired the hosts' comeback when he halved the deficit with a powerful shot three minutes into the second half. Aldo Angoula then headed in a late deserved equaliser.
Valenciennes could only draw against faltering Montpellier, who had Jamel Saihi dismissed for a dangerous tackle in the 57th minute.
Frontman Gregory Pujol had scored from close range for unfancied Valenciennes to cancel out Gaetan Charbonnier's early opener from outside the box. Montpellier are 13th on 14 points.
Mid-table Brest beat Bastia 3-0 while 19th-placed Troyes recovered from two goals down to draw 3-3 at home with basement side Nancy.