Defending champions Castres brought Clermont's four-year 77-match winning home run to a shuddering halt Saturday as a 22-16 victory took them into the French Top 14 semi-finals.
South African scrum-half Rory Kockott played a central role kicking 17 points and setting up his side's only try.
Castres will now face Montpellier in the semi-finals next Saturday.
Defeat brought an end to New Zealander Vern Cotter's eight-year reign as coach of Clermont as he now tries to revive the Scottish international team.
It was Clermont's second successive shattering defeat in the space of two weeks after they had been knocked out of the European Cup in a 46-6 semi-final rout by Saracens.
Clermont were 9-6 to the good at half-time thanks to three penalties from Brock James with Kockott replying with a pair.
Castres gave up eight penalties in an ill-disciplined first half which saw lock forward Capo Ortega and winger Max Evans both sin-binned -- the latter for a deliberate knock-on.
But back to full strength early in the second period, Castres nipped ahead 12-9 as Kockott maintained his 100 percent penalty record.
Clermont lost flanker Gerhard Vosloo to a yellow card for an infringement at the ruck before Castres scored the game's opening try on the hour mark.
Again, Kockott was at the centre of the attention with a dazzling sidestep breaking the Clermont line and immediately forcing the home side onto the back foot.
Ortega stormed towards the posts before being held up. But the momentum was with the champions and a quickly recycled ball allowed centre Remi Lamerat to force his way over for the score.
Kockott added the conversion for 19-9 with the 27-year-old South African turning the screw with another penalty for a 22-9 lead.
Clermont saw a glimmer of hope with four minutes left when No 8 Damien Chouly barged over for a try with James adding the conversion.
But the home side were unable to find the key breakthrough and their challenge ended with a whimper through a knock-on in the last seconds.
On Friday, Irish international fly-half Jonathan Sexton kicked seven penalties from seven attempts to give Racing-Metro a 21-16 win over Toulouse in their quarter-final.
Defeat meant Toulouse's run of 20 successive semi-final appearances came to an end while Sexton's perfect display handed Racing a first ever last-four date and a clash with European champions Toulon next weekend.