The two clubs have played out some hugely entertaining meetings during the past decade, though the results have rarely gone the way of the black, green and gold.
In fact, Saints have won just one of their six clashes with Clermont, with that lone victory coming at the Gardens back in January 2018.
Four of the six matches have been played away from home, at the hugely atmospheric Stade Marcel Michelin, including quarter-finals in the Champions Cup and Challenge Cup.
And now another knockout tie is on the agenda, this time in Northampton, as Phil Dowson's men bid to book their place in the last eight of the Champions Cup once again.
When the draw became clear, Saints boss Dowson reflected on his club's history with Clermont.
"I'm thinking of Teimana Harrison’s hat-trick out there recently (in 2019)," Dowson said.
"It's a great place to play, a huge European club, a great tie for the Saints in the round of 16 to play a club of that nature.
"They will be very well supported and it will be another classic in Europe."
Here's a look back at Saints' six European meetings with Clermont...
1. April 4, 2015: Clermont Auvergne 37 Saints 5
James Wilson in action for Saints in their Champions Cup quarter final defeat at Stade Marcel Michelin. Saints try: Alex Waller (66th minute) Photo: David Rogers
2. October 21, 2017: Clermont Auvergne 24 Saints 7
Dylan Hartley was yellow carded on 30 minutes as Saints were beaten in the Champions Cup pool stage clash at Stade Marcel Michelin. Christian Day scored Saints' only try of the match on 48 minutes, with Harry Mallinder adding the conversion. Photo: David Rogers
3. January 13, 2018: Saints 34 Clermont Auvergne 21
Saints were enduring a torrid campaign but they claimed a stunning win at the Gardens as tries from Teimana Harrison, Nafi Tuitavake, Ben Foden, Ken Pisi and Cobus Reinach got the job done in the Champions Cup pool stages Photo: Tony Marshall
4. October 13, 2018: Saints 20 Clermont Auvergne 41
Saints suffered a heavy home defeat in the pool stages of the Challenge Cup despite late tries from Tom Collins and David Ribbans Photo: Tony Marshall