Former Leeds rugby league star Iestyn Harris wins promotion off the bench and starts at inside-centre instead of Tom Shanklin - while Craig Morgan takes over from injured wing Mark Jones, and Llanelli scrum-half Dwayne Peel is preferred to Gareth Cooper.
Cardiff flanker Martyn Williams will take over from Humphreys as captain, leading Wales for the second time in the tournament - having previously done so in the defeat against Scotland three weeks ago.
If Wales lose then they will suffer their first championship whitewash since 1995.
Wales Team: R Williams (Cardiff); C Morgan (Cardiff), M Taylor (Swansea), I Harris (Cardiff), G Thomas (Bridgend); S Jones (Llanelli), D Peel (Llanelli); I Thomas (Llanelli), M Davies (Pontypridd), G Jenkins (Pontypridd), R Sidoli (Pontypridd), G Llewellyn (Neath), C Charvis (Swansea), M Williams (Cardiff, captain), D Jones (Llanelli).
Replacements: G Williams (Bridgend), M Madden (Llanelli), S Williams (Northampton), G Thomas (Bath), G Cooper (Bath), T Shanklin (Saracens), M Watkins (Llanelli).