Leading 9-3 at the break thanks to three Leigh Halfpenny penalties to Owen Farrell's one, Wales turned up the heat in the second half and Lancaster's side couldn't cope.
Alex Cuthbert crossed the whitewash twice as Dan Biggar kicked eight points and Halfpenny three, ensuring there was no doubt as to where the RBS 6 Nations trophy would be heading.
For and England defeat by six points or less would still have seen Lancaster's side claim the trophy but as soon as Cuthbert scored his first try, the Welsh tide was not going to be stopped.
Having already beaten Scotland, Ireland, France and Italy, crossing the Severn in a bid to win the Grand Slam in the defending champions' backyard proved a whole different proposition for Lancaster's young side - many of whom had never tasted the Millennium Stadium atmosphere.
But Lancaster was adamant that inexperience was not the problem, rather that his side were out-muscled by Wales in the second half.
"We are gutted. We got in at half-time and felt we'd had a decent half," said Lancaster.
"We realised we hadn't got our execution right and we didn't dominate the breakdown and the set-piece was a problem. But we still felt we were going OK.
"But obviously the first quarter of the second half wasn't good enough and Wales thoroughly deserved to win.
"I don't think it was a psychological thing to do with the whole occasion. Wales played well, we didn't turn up and match their physicality. Rugby is a simple game and their physicality was better than ours."