Cross Keys and Llanelli are at home for the opening weekend of matches, Llanelli first to kick off, taking on Connacht Eagles at Parc y Scarlets at 2pm with the Keys hosting Moseley at Pandy Park (3pm).
Principality Premiership champions Pontypridd and Ospreys club Aberavon travel to Scotland to take on Edinburgh Academicals (3pm) and Gala (7pm) respectively.
As part of a move to enable the Welsh clubs to be as competitive as possible in the tournament, and give key players a more intense development platform, the number of Welsh clubs has been reduced from 12 and the four participating clubs have the ability to utilise other players from their region.
Cross Keys head coach Greg Woods said: "It's always tough to take on a fully professional outfit from a pace, power and conditioning point of view but we won't be phased by it.
"We've got pretty much the same side out as usual, with our WRU Dragons Academy boys like Angus O'Brien in the side. But they're all Cross Keys lads and we're at home so it's a key game.
"We've done a review on Moseley, they like to play a lot of rugby and have a very quick back three so we'll have to counter that. We also have to make sure we win the contact area, that's the challenge for us. We have to front up and then hopefully we can start the competition with a bang, but we certainly won't be underestimating them."
Llanelli are using this competition to develop some of their key Academy and Scarlets development players with two sets of brothers involved in the matchday squad. Head coach Kevin George said: "The British & Irish Cup is the next level of competition from the Principality Premiership so we want to give these players the chance to develop and play in these games. Principality Premiership Player of September, 19-year-old Steffan Evans is starting at full back, brothers Adam and Aaron Warren are both starting, along with Wales Under 20 back row Sion Bennett and fellow Under 20 international Carwyn Jones, with his twin brother Llewelyn on the bench.
"We've had some success in the British & Irish Cup in the past and qualified out of our group fairly regularly as well as having some great results out on the road. We're hoping that continues."
Aberavon head coach Simon King added: "We're looking forward to it. We qualified by right and it's a competition we're going into with a great deal of anticipation.
"We've had our squad boosted by some players from the Ospreys. Dan Baker, Sam Davies and Rhodri Hughes will all be involved and we trained well together on Tuesday.
"Aberavon will supply the core of the squad which is right but there are a number of new players who have come in. Our players have responded really well to that challenge and deserve credit for it. From our point of view, it's a positive experience for the club and we're proud to be one of the four teams representing Wales in the British & Irish Cup this year.
"Gala are a strong side, they're second in the Scottish Premiership and are very well drilled. They have a player release system up there so will have players from Edinburgh available and will be a real challenge.
Welsh clubs in British & Irish Cup Round One, Saturday 12 October
2pm Llanelli v Connacht Eagles
3pm Cross Keys v Moseley
3pm Edinburgh Academicals v Pontypridd
7pm Gala v Aberavon