The bookmakers have made Martin Johnson's men an unbackable 1/25 chance, with Wales 7/1 and the draw at 28/1.
Current form reflects those odds, with England arriving in Cardiff on the back of a superb victory over France, while Wales open their campaign by losing to Italy in Rome.
England haven't lost in Cardiff since 1993, and in three previous 6 Nations meetings with Wales, they have won the lot and averaged almost 47 points a time.
Wales coach Steve Hansen has wielded the axe following events at Stadio Flaminio, dropping seven players, including skipper Colin Charvis, fly-half Iestyn Harris and centre Leigh Davies.
But those decisions were nothing when compared to his call from the international wilderness for 33-year-old Bath hooker Jonathan Humphreys.
Humphreys, who made his last Wales appearance during the 1999 World Cup, also takes over as captain, but it is a huge ask for Wales to threaten an England side high on confidence.
England have had their share of injury problems - scrum-half Matt Dawson, props Jason Leonard and Julian White and flanker Lewis Moody are among the absentees - yet they still appear far too strong on paper.
It might not be the landslide victory that many people are predicting, but England's Grand Slam chariot should remain firmly on track by Saturday night.