The Welsh will start favourites as they look to launch their challenge with an opening game victory for the first time since 1997.
But Williams and coach Steve Hansen are aware of the dangers of facing the Azzurri first at the Stadio Flaminio with Italy desperate to add to their solitary success in the tournament on their debut in 2000 against Scotland.
"Italy will be very physical," said Williams, one of six changes to the side beaten by New Zealand last November.
"They are a good side, and they will be looking for some success this season. If we are off our game, then the chances are that we will lose."
Hansen said: "The worst time to play Italy is first up because they have not been deflated by any defeats.
"We have become slow starters in the championship and one reason may be that we lose players to the clubs after the November internationals and only see them again the week before the Six Nations starts."
Wales: R Williams (Cardiff); M Jones (Llanelli), T Shanklin (Saracens), L Davies (Llanelli), G Thomas (Bridgend); I Harris (Cardiff), D Peel (Llanelli); I Thomas (Llanelli), M Davies (Pontypridd), B Evans (Swansea), R Sidoli (Pontypridd), S Williams (Northampton), M Owen (Pontypridd), M Williams (Cardiff), C Charvis (Swansea, capt).
Replacements: G Williams (Bridgend), G Jenkins (Pontypridd), D Jones (Llanelli), G Thomas (Bath), G Cooper (Bath), C Sweeney (Pontypridd), M Watkins (Llanelli).