Victory over the defending champions - who crushed England 30-3 in Cardiff last year - would secure a first triple crown since 2003 for the hosts and propel them into RBS 6 Nations title contention ahead of a trip to Rome to face Italy on the climatic day of this year's tournament.
More than that, it would also land a telling psychological blow ahead of the teams' meeting at the same ground in the pool stage of the 2015 World Cup. Defeat, however, would extend Celtic mastery of the fixture to four successive wins, offer sight of an unprecedented third successive Championship title and damage England's self-belief.
Lancaster, who is seeking his first success against Wales in three attempts, said: "It's a big game and we need to make sure we deliver on the field. All the talking is fine, it's the team that delivers on the day that matters.
"We respect Wales as opponents, the quality and experience they have and how well they are set up. It will be a tough game, but we're ready.
"I understand all the context around this particular game with the World Cup coming and the importance of getting a win. We play Wales twice before the World Cup and Wales play Australia [who are in Group A with England and Wales], so I'm sure psychologically there will be some things there."
England have named Ben Morgan at No.8 in place of the injured Billy Vunipola, who will sit out the rest of the Six Nations with a sprained ankle. Tom Johnson provides back-row cover on the bench.
Six players in total survive from the starting XV for last year's defeat, which denied England the grand slam at the final hurdle. The crushing nature of that result has haunted the England squad since, even though they have gone on to notch notable victories over Australia, Argentina and Ireland.
"You use every defeat as motivation on how to improve," Lancaster said. "We lost to New Zealand in the autumn and that was difficult to take, as was losing to France last month, but we have bounced back from those games and learned, liked we learned from Wales last year. We've moved on since then."
Wales are known for their power-based rugby but Lancaster said: "There's a bit more to their game than people give them credit for. On the day, the gainline's important, but I'd be very surprised if they don't have one or two tricks up their sleeve. They've come up with 12-man lineouts and various other things in the past, so I'm sure there will be things coming our way."
Chris Robshaw, the England captain, believes his team are favourites to prevail - bookmakers agree, installing England as odds-on winners - but Lancaster refuses to give Wales any ammunition before the match. "I don't bet so I don't play the favourites game," he said.
Rob Howley, the Wales assistant coach, agreed that both teams will be driven by clear ambitions. "It is a triple crown [game] for them, and it is a game we want to win to stay in the championship," Howley said. "We've spoken coming into this championship about winning three [titles] in a row.
"This group of players have been together for a period of time now. They have played and won away from home, and that obviously gives you confidence. I suppose it is the side that gains momentum, and then under that pressure of the cauldron of Twickenham, is able to continue the momentum."
Wales have lost the Perpignan lock Luke Charteris to a neck injury sustained during a scrummaging session. He will be replaced by the Scarlets forward Jake Ball who shone on his first Test start in the 27-6 victory over France last month.
"It is a great opportunity for Jake," Howley said. "I thought he was outstanding in the nuts and bolts of his game against France.
TEAMs. England v Wales (Twickenham, tomorrow, 3pm)
England M Brown (Harlequins); J Nowell (Exeter Chiefs), L Burrell (Northampton Saints), B Twelvetrees Gloucester), J May (Gloucester); O Farrell (Saracens), D Care (Harlequins); J Marler (Harlequins), D Hartley (Northampton Saints), D Wilson (Bath), J Launchbury (Wasps), C Lawes (Northampton Saints), T Wood (Northampton Saints), C Robshaw (Harlequins, capt), B Morgan (Gloucester)
Substitutes T Youngs (Leicester Tigers), M Vunipola (Saracens), H Thomas (Sale Sharks), D Attwood (Bath), T Johnson (Exeter Chiefs), L Dickson (Northampton Saints), G Ford (Bath), A Goode (Saracens)
Wales L Halfpenny (Cardiff Blues); A Cuthbert (Cardiff Blues), J Davies (Scarlets), J Roberts (Racing Metro), G North (Northampton Saints); R Priestland (Scarlets), R Webb (Ospreys); G Jenkins (Cardiff Blues), R Hibbard (Ospreys), A Jones (Ospreys), L Charteris (Perpignan), A-W Jones (Ospreys), D Lydiate (Racing Metro), S Warburton (Cardiff Blues, capt), T Faletau (Newport Gwent Dragons)
Substitutes K Owens (Scarlets), P James (Bath), R Jones (Scarlets), J Ball (Scarlets), J Tipuric (Ospreys), M Phillips (Racing Metro), D Biggar (Ospreys), L Williams (Scarlets)
Referee Romain Poite (France)
Assistant referees Steve Walsh (Australia) & Lourens van der Merwe (South Africa)