Exeter, Harlequins and London Irish all face trips to South African sides, included in the competition for the first time, in the pool stages of the 2022-23 Heineken Champions Cup.
In Pool A Exeter face Pretoria-based Bulls and French side Castres, while Harlequins face Durban-based Sharks and Racing 92 of Paris.
In Pool B London Irish take on United Rugby Championship winners Stormers and French champions Montpellier, while defending champions La Rochelle meet Northampton and Ulster.
The French side beat Leinster in May to win the competition for the first time.
Wales' only Champions Cup representatives, Ospreys, will face the champions of France and England, Montpellier and Leicester, in Pool B.
Edinburgh meet Castres and Saracens.
Champions Cup organisers have said the inclusion of the three South African sides will bring "a new level of elite rugby".
Two other South African sides, Lions and Cheetahs, will play in the second-tier Challenge Cup.
Worcester will travel to South Africa to face the Johannesburg-based Lions.
Bath have arguably the toughest draw of England's five Challenge Cup representatives, facing Toulon and Glasgow.
How it works
The Champions Cup is the top-tier competition for clubs from England's Premiership, France's Top 14 and the United Rugby Championship, in which sides from Ireland, Italy, Scotland, Wales and South Africa compete.
The 2022-23 Champions and Challenge Cup season will be played over eight weekends, with four rounds of matches in the pool stage and the opening round of fixtures in both competitions taking place on the weekend of 9-11 December.
In the new format, each team has been drawn to face two opponents, home and away. However, those two opponents do not in turn face each other in a closed mini-league of three; they have their own two teams to face. So, in the draw set out below, Castres will play Exeter and Edinburgh home and away, but Exeter will face Castres and Bulls, Bulls will face Exeter and Lyon, and so on.
The organiser European Professional Club Rugby sets out the rationale for which sides are drawn together here.
At the end of the four rounds of pool games, the top eight teams in each pool progress to a last-16 stage, followed by quarter-finals, semi-finals and finals - which will be played at the Aviva Stadium in Dublin - the Challenge Cup decider on Friday 19 May and the Champions Cup final the following day.
Castres Olympique v Exeter Chiefs and Edinburgh Rugby
Saracens v Lyon and Edinburgh Rugby
Bulls v Lyon and Exeter Chiefs
Bordeaux-Bègles v Gloucester and Sharks
Harlequins v Racing 92 and Sharks
Leinster v Racing 92 and Gloucester
Racing 92 v Harlequins and Leinster Rugby
Gloucester v Bordeaux-Begles and Leinster
Sharks v Bordeaux-Bègles and Harlequins
Lyon v Saracens and Bulls
Exeter Chiefs v Castres and Bulls
Edinburgh v Castres and Saracens
Montpellier v London Irish and Ospreys
Leicester Tigers v Clermont Auvergne and Ospreys
Stormers v Clermont Auvergne and London Irish
Toulouse v Sale Sharks and Munster
Northampton Saints v La Rochelle and Munster
Ulster v La Rochelle and Sale Sharks
La Rochelle v Northampton and Ulster
Sale Sharks v Toulouse and Ulster
Munster v Toulouse and Northampton
Clermont Auvergne v Leicester and Stormers
London Irish v Montpellier and Stormers
Ospreys v Montpellier and Leicester
Glasgow Warriors v Perpignan and Bath
Toulon v Zebre and Bath
Bristol v Zebre and Perpignan
Connacht v Brive and Newcastle
Cardiff v Brive and Newcastle
Brive v Connacht and Cardiff
Newcatle v Connacht and Cardiff
Perpignan v Bristol and Glasgow Warriors
Zebre v Bristol and Toulon
Bath v Toulon and Glasgow Warriors
Scarlets, Bayonne and Cheetahs
Pau v Dragons and Cheetahs
Wasps v Dragons and Bayonne
Lions v Stade Francais and Worcester Warriors
Benetton v Stade Francais and Worcester Warriors
Stade Francais v Lions and Benetton
Worcester Warriors v Lions and Benetton
Dragons v Pau and Wasps
Toulon v Scarlets and Wasps
Cheetahs v Scarlets and Pau