Friday will be the second competitive fixture between the two sides since Championship clubs were invited into the Premiership Rugby Cup last season.
Pirates were beaten 38-13 at Sandy Park last September and defeated 46-24 at the same venue in a pre-season game in late August this year.
You have to go back to February 2010 for the last time Pirates beat Exeter in a competitive game when a 34-17 win at Camborne helped them top the group in the British and Irish Cup.
Pirates would go on to win the trophy that year while Exeter overcame Bristol over two legs to win the Championship play-off final and their place in the top flight.
It is 17 years since Exeter were beaten by their Cornish rivals in a league game – a 30-23 reverse in October 2007 that came just a few months after the Pirates had beaten the Chiefs 19-16 in the National Trophy final at Twickenham.
“Over the years it’s been tough there,” Exeter director of rugby Rob Baxter tells BBC Radio Devon.
“I’ve played in a few wins and I’ve played in a few losses myself, and I’ve coached some wins and I’ve coached some losses.
“We always really celebrated those wins because they were big wins when we were both in the Championship – the Cornish Pirates were a good side, probably funded beyond us for quite a while
“Then we slowly turned that tide and so this will be a good challenge as well.”
With Exeter’s poor run of form in the Premiership, the relatively local trip to Cornwall presents a big chance for Baxter’s side to try and get back to winning ways against a struggling team from the league below.
“It’ll be a challenge for us particularly because of where we are at the moment,” he added. “But at the same time sport is what it is and you’ve got to get on with it.
“I’m still pretty positive and pretty hopeful, that myself and some of the players and coaches will look back on this five or six week period, and I’m not going to say look on it with fondness because there’s nothing to look back on with fondness, but we’ll look back on it and go ‘remember that, we came through it’.
“It doesn’t take long memory to to know that you can turn round things fairly quickly if you get things right.
“Sometimes you have to work through these things right here and now and they don’t always result in victories, but you have to get yourself back on the front foot and on a development pathway and that’s what we’re going to aim to do.”