All four will be facing Aviva Premiership opposition as they look to kick-off their Cup campaigns with a bang.
Joining the competition 12 years ago, the Welsh regions have enjoyed the sweet taste of victory with Cardiff Blues and the Ospreys both lifting the trophy, while each region has made the final-four at least once.
But while a Welsh region made the semi-finals in each of the first seven editions of the tournament, none have made it out of their group in the last four.
Here we take a look at who each of the Welsh sides will be up against from England.
Scarlets v Exeter Chiefs
Favourites to cause a stir this season in the Anglo-Welsh Cup are surely the Scarlets.
Last season’s domestic champions will be missing a key number of internationals during the autumn window.
But their form this season domestically has been spectacular, beginning the defence of their crown with seven wins from their first eight games.
And they have a fine track record in this competition – making it all the way to the final in the inaugural staging back in 2005/06.
Their opening encounter could not be more enticing as they prepare to take on Aviva Premiership champions Exeter Chiefs at Parc Y Scarlets. Fourteen of their starting XV named are aged 25 or under, with teenage winger Tom Rogers the youngest in the matchday 23.
Tighthead prop Simon Gardiner and lock Tom Price bring league and European experience to the side.
The Chiefs made the perfect start to the campaign having brushed aside Northampton Saints in Round 1 as they go in search of their fourth successive Anglo-Welsh Cup final.
— Scarlets Rugby (@scarlets_rugby) November 10, 2017
Ospreys v Wasps
The Ospreys won this competition back in 2007/08, beating the powerhouse Leicester Tigers in the final and gaining revenge for their defeat at Twickenham 12 months previously.
They would love to repeat those heroics a decade on but their start to the season has been stuttering.
They currently sit bottom of Conference A in the Guinness PRO14 with only two wins from their first eight games.
But they will take heart from their European showings that saw them grab losing bonus points against both Saracens and Clermont – the two finalists from last season.
Ospreys will take on Wasps at Liberty Stadium in what will be the first cross-border clash of the competition, and hand Will Jones, Morgan Morris and Tom Williams debuts with five more uncapped players on the bench.
Wasps have named another inexperienced side following their 53-41 defeat at the hands of Newcastle Falcons.
— Ospreys (@ospreys) November 9, 2017
Newcastle Falcons v Cardiff Blues
The last Welsh region to lift this trophy was the Cardiff Blues back in the 2008/09 season.
That year they blew Gloucester Rugby away at Twickenham for a fantastic victory – the icing on a fine season that also saw them reach the European semi-finals.
A year later they made the semi-finals again, as the Cherry & Whites claimed revenge for their final defeat.
This time around, the Blues have named an youthful line-up for their opening match against the Newcastle Falcons who are looking to build on their good domestic form, but experienced lock, George Earle, will lead the side at Kingston Park.
20 Welsh qualified players
16 Cardiff Blues pathway graduates
16 Players 25 or younger
2 Potential debutants pic.twitter.com/9f3pU4vHH6
— Cardiff Blues (@cardiff_blues) November 10, 2017
Northampton Saints v Dragons
Dragons made the semi-finals in the 2010/11 campaign but lost to eventual champions Gloucester.
Since then they have failed to make it out of the group stages but this season they will be hoping to end that run.
And their Anglo-Welsh campaign this season sees them begin with a trip to Franklin’s Gardens to take on the Northampton Saints.
Wing Ashton Hewitt will skipper the side, with full-back Joe Goodchild selected for his first senior match and on-loan signing Joe Thomas getting the nod in the centres.
The Saints have been had an indifferent start to their league campaign, winning four and losing three, but will be looking to bounce back from their defeat at the hands of Exeter last time out in this competition.
— Dragons Rugby (@dragonsrugby) November 10, 2017
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