Ospreys will kick off the 2012-13 Heineken Cup campaign when they host Italian outfit Benetton Treviso.
The reigning RaboDirect Pro12 champions are the first Welsh region in action when they play at the Liberty Stadium on Friday, 12 October.
Scarlets travel to face ASM Clermont Auvergne at the Stade Marcel Michelin on Saturday, 13 October.
And Cardiff Blues play Sale Sharks at the Salford City Stadium the following day.
Treviso recorded a 26-26 draw in their Heineken Cup Pool game against Ospreys last season, costing the Welsh side a quarter-final place.
Fly-half Matthew Morgan, on his Heineken Cup debut, salvaged a draw in a Pool clash with a dramatic last-minute penalty at the Stadio Comunale di Monigo.
Ospreys' other Pool Two opponents are European heavyweights Toulouse and Leicester, who boast six Heineken Cup crowns between them.
For Steve Tandy, it will be his first European campaign as a coach of the Welsh region.
"We'll be going head to head with two of the great Heineken Cup clubs in Leicester and Toulouse while Treviso will have a huge say in who progresses from Pool Two," said Tandy.
"There will be six tough games, impossible to predict, everything that the Heineken Cup is about.
"It's four teams who are each capable of beating each other on their day, so it's important that we get off to a good start."
Ospreys are unbeaten in the last three Heineken Cup fixtures against Leicester, have lost twice to Toulouse and are unbeaten in four games against Treviso despite the 26-26 draw in Italy last October.
Simon Easterby, the Scarlets new coach, who was appointed this summer, has demanded his side hit the ground running in Europe.
The Scarlets, who reached the quarter-finals of last season's Amlin Challenge Cup, will face a tough test when they travel to play former centre Regan King's Clermont, who were last season's Heineken Cup semi-finalists.
"This certainly gives us a huge focus to hit our top form in round one," said Easterby.
"You don't get two rounds much tougher than these and while the odds may be stacked against us, that could work in our favour.
"We know we can bring form to big away games as underdogs and these big European occasions can be lifted by a great travelling Scarlets support too - I'm sure many down West remember Toulouse away five years ago."
Scarlets are in the same Pool 5 as Clermont, reigning champions Leinster and tournament new boys, Exeter Chief.
Phil Davies' new look Cardiff Blues, who lost a dozen players in the summer, will travel to Sale Sharks for their Pool opener.
They will then welcome former favourite Gethin Jenkins back to the Arms Park when Toulouse are the visitors a week later on 21 October.
The competition will venture into Belgium for the first time when the 2011 English champions, Saracens, take their round two match against Racing Metro 92 on Saturday, 20 October to the 50,000-capacity King Baudouin Stadium in Brussels.
HEINEKEN CUP FIXTURES (All kick-offs local time)
FRIDAY, 12 OCTOBER 2012
Pool 2 Ospreys v Benetton Treviso, Liberty Stadium (20.00)
Pool 4 Ulster Rugby v Castres Olympique, Ravenhill (20.00)
SATURDAY, 13 OCTOBER 2012
Pool 1 Edinburgh Rugby v Saracens, Murrayfield (13.35)
Pool 1 Racing Metro 92 v Munster Rugby, Stade de France (14.35)
Pool 3 Zebre v Connacht Rugby, Stadio XXV Aprile (Parma) (14.35)
Pool 5 Leinster Rugby v Exeter Chiefs , RDS (15.40)
Pool 5 ASM Clermont Auvergne v Scarlets, Stade Marcel Michelin (16.40)
Pool 3 Harlequins v Biarritz Olympique, Twickenham Stoop (18.00)
SUNDAY, 14 OCTOBER 2012
Pool 4 Northampton Saints v Glasgow Warriors, Franklin's Gardens (12.45)
Pool 6 Sale Sharks v Cardiff Blues, Salford City Stadium (12.45)
Pool 2 Toulouse v Leicester Tigers, Le Stadium (16.00)
Pool 6 Toulon v Montpellier, Stade Felix Mayol (21.00)
FRIDAY, 19 OCTOBER 2012
Pool 4 Glasgow Warriors v Ulster Rugby, Scotstoun Stadium (20.00)
Pool 4 Castres Olympique v Northampton Saints, Stade Pierre Antoine (21.00)
SATURDAY, 20 OCTOBER 2012
Pool 5 Scarlets v Leinster Rugby, Parc y Scarlets (13.35)
Pool 2 Benetton Treviso v Toulouse, Stadio Comunale di Monigo (14.35)
Pool 1 Saracens v Racing Metro 92, King Baudouin Stadium (Brussels) (16.40)
Pool 3 Connacht Rugby v Harlequins, The Sportsground (18.00)
Pool 5 Exeter Chiefs v ASM Clermont Auvergne, Sandy Park (18.00)
Pool 3 Biarritz Olympique v Zebre, Parc des Sports Aguilera (19.00)
SUNDAY, 21 OCTOBER 2012
Pool 1 Munster Rugby v Edinburgh Rugby, Thomond Park (12.45)
Pool 6 Cardiff Blues v Toulon, Cardiff Arms Park (12.45)
Pool 2 Leicester Tigers v Ospreys, Welford Road (15.00)
Pool 6 Montpellier v Sale Sharks, Stade Yves du Manoir (16.00)
FRIDAY, 7 DECEMBER 2012
Pool 4 Glasgow Warriors v Castres Olympique, Scotstoun Stadium (19.35)
Pool 3 Connacht Rugby v Biarritz Olympique, The Sportsground (20.00)
Pool 4 Northampton Saints v Ulster Rugby, Franklin's Gardens (20.00)
SATURDAY, 8 DECEMBER 2012
Pool 5 Scarlets v Exeter Chiefs, Parc y Scarlets (13.35)
Pool 2 Toulouse v Ospreys, Stade Ernest Wallon (14.35)
Pool 3 Zebre v Harlequins, Stadio XXV Aprile (14.35)
Pool 2 Leicester Tigers v Benetton Treviso, Welford Road (15.40)
Pool 6 Sale Sharks v Toulon, Salford City Stadium (15.40)
Pool 1 Munster Rugby v Saracens, Thomond Park (18.00)
Pool 1 Racing Metro 92 v Edinburgh Rugby, Stade Yves du Manoir (19.00)
SUNDAY, 9 DECEMBER 2012
Pool 6 Cardiff Blues v Montpellier, Cardiff Arms Park (12.45)
Pool 5 ASM Clermont Auvergne v Leinster Rugby, St Marcel Michelin (16.00)
FRIDAY, 14 DECEMBER 2012
Pool 1 Edinburgh Rugby v Racing Metro 92, Murrayfield (20.00)
Pool 3 Biarritz Olympique v Connacht Rugby, Parc des Sports Aguilera (21.00)
SATURDAY, 15 DECEMBER 2012
Pool 2 Ospreys v Toulouse, Liberty Stadium (13.35)
Pool 2 Benetton Treviso v Leicester Tigers, Stadio di Monigo (14.35)
Pool 3 Harlequins v Zebre, Twickenham Stoop (15.00)
Pool 5 Leinster Rugby v ASM Clermont Auvergne, Aviva Stadium (15.40)
Pool 5 Exeter Chiefs v Scarlets, Sandy Park (15.40)
Pool 4 Ulster Rugby v Northampton Saints, Ravenhill (18.00)
Pool 6 Montpellier v Cardiff Blues, Stade Yves du Manoir (19.00)
SUNDAY, 16 DECEMBER 2012
Pool 4 Castres Olympique v Glasgow Warriors, Stade Pierre Antoine (13.45)
Pool 1 Saracens v Munster Rugby, London venue (TBC) (15.00)
Pool 6 Toulon v Sale Sharks, Stade Felix Mayol (16.00)