Toulouse fly-half David Skrela kicked six penalty goals to hand the defending champions a close 18-16 Heineken Cup win over Wasps on Sunday.
Wasps scored the only try through substitute David Lemi in the second period while David Walder had the chance to win the tie with a last-gasp penalty.
But the fly-half pulled his kick wide of the posts and four-time champions Toulouse held on.
Wasps were back in Europe's premier competition after a one-year absence but Tony Hanks' side suffered the same fate as in their previous appearance in January 2009 - a defeat in France.
On that occasion it was Castres but this time they faced a stiffer test against the reigning holders, who beat Biarritz in Paris last May.
Wasps suffered a blow when England centre Riki Flutey pulled out due to the impending birth of his third child. But the greasy conditions almost helped Wasps take a shock lead inside 68 seconds.
Ben Jacobs hacked ahead but the ball spiralled out of play before the centre could claim his hands on the ball. Wasps took the lead in the fourth minute courtesy of a Walder penalty from close-range.
Both sides were unable to find any cohesion in the wet but Toulouse levelled on 11 minutes when fly-half Skrela fired home a routine penalty.
Fly-half Walder quickly replied with his second successful kick before Skrela was fortunate when his next effort hit the bar and bounced over to tie the scores at 6-6.
After a ragged opening quarter, Toulouse stepped up the intensity and should have grabbed the first try of the match on 24 minutes only for full-back Clement Poitrenaud to drop the ball with the try-line at his mercy.
Skrela saw his previous good luck desert him when he crashed another penalty against the left up-right but he made no mistake to put the French giants ahead for the first time on 31 minutes.
Wasps refused to buckle and after a quick-tap by skipper Tom Rees, Walder calmed slotted home a fine drop goal to head into the interval all square at 9-9.
Toulouse dominated possession for large periods in the second half but Guy Noves' men were forced to wait until the hour mark to regain the lead when Skrela added his fourth penalty.
He added a fifth to extend the hosts' lead to six points before the game's talking point.
Walder kicked through and after Poitrenaud hesitated, replacement Lemi kicked ahead twice before touching down. Clancy failed to award the spot the Samoan wing's hand on the ball but, at the first stoppage in play, the official asked for the television match official who, after viewing a replay, gave the green light for the opening try of the match.
Walder added the conversion from in front of the posts and Wasps were ahead.
But the lead was short-lived as the visitors were penalised at a scrum and Skrela took advantage.
Walder had the chance to seal a famous win for the Aviva Premiership outfit in the final seconds but his attempt was off target.
Pens: Skrela 6
Pens: Walder 2
Toulouse: 15 ClÃ©ment Poitrenaud, 14 Vincent Clerc, 13 Florian Fritz, 12 Yannick Jauzion, 11 CÃ©dric Heymans, 10 David Skrela, 9 Byron Kelleher, 8 Shaun Sowerby, 7 Thierry Dusautoir, 6 Yannick Nyanga, 5 Romain Millo-Chluski, 4 GrÃ©gory Lamboley, 3 Census Johnston, 2 William Servat, 1 Jean-Baptiste Poux.
Replacements: 16 Virgile Lacombe, 17 Daan Human, 18 Yohan Montes, 19 Yoann Maestri, 20 Nicolas Bezy, 21 Nicolas Vergallo, 22 Maxime Medard, 23 Louis Picamoles ,
Wasps: 15 Mark Van Gisbergen, 14 Richard Haughton, 13 Ben Jacobs, 12 Dominic Waldouck, 11 Tom Varndell 10 Dave Walder, 9 Joe Simpson,8 Andy Powell 7 Tom Rees (c) 6 Joe Worsley 5 Richard Birkett 4 Simon Shaw 3 Ben Broster 2 Joe Ward 1 Zak Taulafo
Replacements:16 Rob Webber, 17 Charlie Beech, 18 Jason Hobson, 19 James Cannon, 20 Dan Ward-Smith, 21 Nic Berry, 22 Riki Flutey, 23 David Lemi.
Referee: George Clancy