The Manchester United man had scored 8 goals in his last 13 games for club and country.
With both sides tied on 11 points at the top of Group B in the Euro 2016 qualifying, players and supporters will be aware that the victors at the Millennium Stadium will be favourites to reach France next summer.
Fellaini's absence is a huge blow for Marc Wilmots side, with the former Everton man a match winner in Belgium's recent win over France.
A groin problem suffered in training by the 27-year-old has meant the Red Devils are without one of their most important attacking weapons for the top of the table clash between Belgium and Wales in Cardiff, as Wilmots tweeted yesterday.
The Manchester United man scored with two first-half goals in the Paris win on Sunday, first netting a close range strike and then a trademark header, also assisting midfielder partner Radja Nainggolan to make it 3-0 in before the break.
He came off in the 77th minute for Spurs winger Nacer Chadli, with Belgium 4-1 up, so is absolved of France's late comeback attempts that left the score at 4-3 to the visitors. It is likely another Tottenham midfielder, Moussa Dembele, will deputise in Cardiff.
Fellaini starred for United this season under Louis van Gaal, often playing in an advanced midfield position where he could do damage with his physical presence and aerial ability.
He scored 7 times in 31 appearances in the season just gone, playing a vital role as United secured their Champions League return.