Roberto Martinez's men won their opening match 3-0 away to Iceland, but are still second as their guests thrashed the same opposition 6-0 in their first group game.
Having lost just once in 28 fixtures, they are 2/5 (1.40) favourites with 888Sport to leapfrog them into first place by coming out on top in Brussels.
Just one of the previous seven encounters between this pair has resulted in a draw, but there are odds of 7/2 (4.50) available on them cancelling each other out in this one.
With Mousa Dembele, Jan Vertonghen, Kevin De Bruyne and Adnan Januzaj all injured, Martinez has recalled Jason Denayer, Christian Kabasele and Dennis Praet, as well as giving Brandon Mecehel a first call-up.
Kevin Mbabu, Johan Djourou and Admir Mehmedi are all absent through injury for Vladimir Petkovic, who has called up uncapped Young Boys midfielder Christian Fassnacht.
As a side hardly renowned for attacking football, it was a surprise to see Switzerland put six goals past Iceland in their Nations League opener.
Petkovic's men were knocked out of the World Cup in a drab 1-0 defeat to Sweden in their previous game, and were subsequently beaten 1-0 by England in a similarly uninspiring friendly encounter just three days after demolishing Iceland.
A similar display seems likely against Les Diables Rouges, who have won three consecutive games without conceding a goal and kept clean sheets in six of their last eight matches on home turf.
All in all, odds of 7/5 (2.40) are well worth backing on a classy Belgium winning to nil in a straightforward victory over Switzerland.