Johann Muller will once again lead an all-international pack, in which loose forwards Stephen Ferris, Chris Henry and Pedrie Wannenburg have been in excellent form.
Ulster's match winners against Leicester, Ruan Pienaar and Andrew Trimble, will be instrumental to Ulster's hope of victory this time out. Stefan Terblanche gets the nod over Adam D'Arcy at fullback.
Apart from the inclusion of Spence, the only other change among the replacements is Andi Kyriacou coming in for Nigel Brady. The hooker will earn his 50th cap for the Province if he gets any time on the pitch.
Ulster face a difficult task in their 100th European tie. They have never won in France in 14 attempts, while their hosts on Saturday are unbeaten at home in 38 matches. But Ulster will be buoyed by the performance against Leicester last week and are determined to create history by making the knockout stages in two consecutive years for the first time in their history.
Attack coach Neil Doak said: "This weekend is all about clearing the next hurdle in our progression. It was great to reach the quarter-finals last year and be highly competitive against Northampton Saints, but the game in Clermont is much bigger than last year's quarter-final.
"We've got to go and get the monkey off our back by winning in France for the first time and we want to put ourselves in with a chance of a home draw in the last eight. Munster and Leinster are already there and it would be great for Irish rugby if we had three provinces in the quarter-finals for the first time. We have been building nicely towards this game and the players all know how important it is."
Ulster Match Day Squad to face ASM Clermont Auvergne, Saturday 21st January 2012, Stade Marcel Michelin (kick-off 3.40pm GMT):
(15-9): S Terblanche; A Trimble, I Whitten, P Wallace, C Gilroy; I Humphreys, R Pienaar;
(1-8): T Court, R Best, J Afoa, J Muller (capt), D Tuohy, S Ferris, C Henry, P Wannenburg;
Replacements (16-23): A Kyriacou, C Black, A Macklin, L Stevenson, W Faloon, P Marshall, N Spence, A D'Arcy
Unavailable due to injury: Jared Payne (achilles), Declan Fitzpatrick (neck), Peter Nelson (knee), Darren Cave (foot)
ASM Clermont Auvergne Squad:
(15-9): L Byrne; S Sivavatu, A Rougerie (capt), W Fofana, J Malzieu; D Skrela, M Parra;
(1-8): L Faure, B Kayser, C Ric, J Pierre, N Hines, G Vosloo, J Bardy, J Bonnaire;
Replacements (16-23): T Paulo, V Debaty, D Kotze, J Cudmore, A Lapandry, K Senio, B James, R King