Faletau was poised to make his first appearance since suffering a shoulder injury at March against Leinster last weekend.
The Wales number eight, 35, took part in the warm-up in Dublin but the Blue and Blacks opted not to risk him due to niggles.
Faletau starts in Northampton while wing Josh Adams is on the bench and set for his first appearance since facing Argentina in July.
Tonga forward Semisi Paea makes his first start at blind-side flanker, with on-loan Leicester lock Tom Manz given a debut.
Wales fly-half Jarrod Evans starts for the first time since returning to the club from Harlequins in the summer.
He will marshall a back line that features three promising prospects wing Tom Bowen, centre Steffan Emanuel and full-back Matty Young.
The schedule cannot dim Cardiff's excitement about testing themselves against Europe's best teams after finishing sixth in the URC and making the play-offs last season.
"On Monday morning there was a sense of excitement around the place," said Van Zyl.
"There was a lot of hard work to get to the Champions Cup, so these are exciting times.
"There are massive challenges, but that's what we want to be as a club, to compete against the best.
"It has been two seasons and we worked hard last season, so this is the reward to have the opportunity play in special occasions."
Cardiff host Bath in December and then face a pair of French teams in January, travelling to Stade Francais and entertaining Montpellier.
Northampton: Pater; Sleightholme, Hutchinson, Thame, Hendy; Belleau, Mitchell; Fischetti, Smith, Kundiona, Lockett, van der Mescht, Kemeny, Taylor, Chick.
Replacements: Langdon, Els, Neculai, Prowse, Ulcoq, McParland, Smith, Dingwall.
Cardiff: Young; Grady, Millard, Emanuel, Bowen; Evans, A Davies; Southworth, D Hughes (capt), Wainwright, Manz, Thornton, Paea, D Thomas, Faletau.
Replacements: E Lloyd, Barratt, Cowell, McNally, De La Rua, Mulder, Sheedy, Adams.
Referee: Jeremy Rozier (France)
Assistant referees: Thomas Charabas (France) & Cyrille Boulay (France)
TMO: Julien Castaignede (France)
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