The first round of the group stage began on 12 October 2018, and the competition will end with the final on 10 May 2019 in Newcastle upon Tyne, United Kingdom.

The two Russian teams who had competed in the 2017–18 tournament played each other in a two-legged qualifying play-off for a place in the Challenge Cup.

However, they were ruled ineligible by EPC Rugby due to their primary financial backer, Hans-Peter Wild, also being the majority shareholder in Stade Français and therefore being in a position to influence two teams in the competition.

[3] Timișoara Saracens, who had been eliminated by Heidelberger RK at the Continental Shield semi-final stage (effectively the Challenge Cup play-off) were confirmed as their replacement on 11 June 2018.

Note: Placing shown in brackets, denotes standing at the end of the regular season for their respective leagues, with their end of season positioning shown through CH for Champions, RU for Runner-up, SF for losing Semi-finalist and QF for losing Quarter-finalist.

Teams in the same pool play each other twice, both at home and away in the group stage started in October 2018, and continues through to January 2019.

[8] In the event of a tie between two or more teams, the following tie-breakers will be used, as directed by EPCR: The eight qualifiers are ranked according to their performance in the pool stage and compete in the quarter-finals which will be held on the weekend of 28–31 March 2019.

However, beginning this season the higher-seeded team will host each semi-final regardless of whether they won their quarter-final at home or on the road.