The Toulon prop, who has won 97 caps, suffered a calf muscle injury during the 26-9 victory over Italy in Rome 10 days ago and will be replaced by Bath forward Paul James.
Two other changes from that game see flanker Sam Warburton - last season's Grand Slam captain - return to the starting line-up instead of Justin Tipuric, while lock Alun-Wyn Jones replaces Andrew Coombs, but even though Warburton has been recalled following a shoulder injury earlier in the championship, his back-row colleague Ryan Jones remains as skipper.
Jones, who has captained Wales a record 31 times, took over from Warburton when Wales beat France in Paris, and he unsurprisingly keeps the job this weekend.
Wales' interim head coach Rob Howley retains the same back division for a fourth successive game, but three changes on the bench from Rome see Cardiff Blues prop Scott Andrews come in for James, with Coombs and Tipuric swapping places with Jones and Warburton respectively.
"Ryan has led the team to two wins and deserves to captain the side against Scotland," Howley said. "We have spoken a lot about momentum in this tournament, and we go into the game with two wins under our belt, but Scotland are in the same position and it's going to be a good challenge."
It will be Alun-Wyn Jones' first Test start since he suffered a shoulder injury against Argentina last November and subsequently underwent surgery. It is a tough call on Newport Gwent Dragons forward Coombs, whose performances in the Six Nations so far have impressed, but Jones offers considerable experience, having won almost 70 caps.
L Halfpenny (Cardiff Blues); A Cuthbert (Cardiff Blues), J Davies (Scarlets), J Roberts (Cardiff Blues); G North (Scarlets); D Biggar (Ospreys), M Phillips (Bayonne); P James (Bath), R Hibbard (Ospreys), A Jones (Ospreys), A-W Jones (Ospreys), I Evans (Ospreys), R Jones (Ospreys, capt), S Warburton (Cardiff Blues), T Faletau (Newport Gwent Dragons).
Replacements: K Owens (Scarlets), S Andrews (Cardiff Blues), C Mitchell (Exeter), A Coombs (Newport Gwent Dragons), J Tipuric (Ospreys), L Williams (Cardiff Blues), J Hook (Perpignan), S Williams (Scarlets).
- Sports & Recreation
- Sam Warburton