The Red Rose had gone 10-0 down thanks to an early Rob Evans try and five points from the boot of Dan Biggar, but Burrell’s score breathed new life into Eddie Jones’ men.
And though Biggar added another penalty, further England scores from Anthony Watson, Ben Youngs, Jack Clifford and Marland Yarde earned a comfortable victory.
If George Ford had landed his kicks it would have been a walk in the park for the men in white, as the Bath man only hit the target with one of his seven attempts.
But it didn’t matter as England secured the win in the Old Mutual Wealth Cup match, which saw a debut for Saints flanker Teimana Harrison, who started at six.
Harrison’s joy was mirrored by Burrell as the big centre registered his first England try since the 29-18 Six Nations win against Wales at Twickenham in March, 2014.
Dylan Hartley and Courtney Lawes were also heavily involved in this victory, with the former skippering England.
And Paul Hill also got some game time, coming off the bench for the final 12 minutes, with England cruising to the win.
The only Saints man to suffer disappointment was George North, who played the full game for Wales on the wing.
But it had all started so well for North and Co as prop Evans used his power to shrug off Clifford to score.
Biggar converted with ease and Wales were again at the England door soon after as Lawes conceded a penalty that allowed the men in red to go for the corner.
Burrell was then penalised for not releasing and Biggar decided to take the points, putting Wales 10-0 up inside the first 15 minutes.
Ford had the chance to respond with a fairly simple penalty, but he spurned the opportunity, prompting groans from the home fans.
But England were to get on the scoreboard soon after, and it was Burrell who did the business.
The Saints centre, who had been victorious in all of his five previous appearances for England at Twickenham, ran a lovely line and bulldozed Biggar to score on his first appearance for his country since August, 2015.
Ford fluffed the conversion and Biggar was doing a better job at the other end, adding another penalty to his team’s tally.
But again England issued a riposte and wing Watson showed great balance and poise to grab his side’s second try as he evaded Liam Williams before stretching to score.
Ford missed his third kick from as many attempts, sending the conversion to the right of the posts and that left England three points behind at the break.
But they were to lead for the first time five minutes into the second period as Youngs picked up the ball from a lineout and weaved his way through for the score.
Ford’s difficult day continued as he missed the conversion, but England were starting to ramp it up though, and Wales were wilting in the Twickenham heat as Clifford sprinted clear to score.
Wales were furious at the award of the try, with Biggar taking particular issue, feeling Dan Cole had knocked on in the build-up.
But referee Marius Mitrea waved away the protests and Ford converted to bring the biggest cheer of the afternoon from the Twickenham faithful.
Wales were now under real pressure and Lawes was the architect of England’s third second-half score.
The Saints second row smashed Jamie Roberts, picked himself up to hit him again and then, after England won the ball back, Lawes offloaded superbly to Yarde, who scored.
It was to be Lawes’ final act as he was replaced after a big shift and Ford then missed the conversion.
The fly-half missed his sixth kick from seven attempts seven minutes from time as Hartley decided his team should go for goal.
But luckily for Ford, his abundance of missed kicks wasn’t going to cost England as they proceeded to canter to victory.
England: Brown; Watson, Joseph (Daly 68), Burrell, Yarde; Ford (Devoto 75), B Youngs (Care 56); Mullan (Genge 66), Hartley (c) (Taylor 76), Cole (Hill 68); Launchbury, Lawes (Attwood 62); Harrison, Haskell (Kvesic 62), Clifford.
Wales: L Williams, North, S Williams (Anscombe 56), Roberts, Amos; Biggar (Priestland 56), Webb; R Evans (Jenkins 56), Baldwin (Dacey 56), Lee; Ball, Wyn-Jones (Turnbull 57); Moriarty, Lydiate (King 22), Faletau.
Referee: Marius Mitrea