Headed goals from Daniel Sturridge, Adam Lallana and Gary Cahill saw England to their biggest victory in more than a year.
After a fiercely competitive start to this 2018 World Cup qualifier Sturridge opened the scoring midway through the first half.
And, after the interval, Lallana scored his first goal at Wembley Stadium before Cahill saw England to the same margin of victory as they recorded against Lithuania in October 2015.
The Three Lions were simply too strong for the Auld Enemy and, at the back, a fourth successive clean sheet ensured England cemented their spot at the top of Group F, two points clear of Slovenia.
Interim manager Gareth Southgate made three changes to the side that started the goalless draw with Slovenia last month.
The three behind lone striker Sturridge – Raheem Sterling, captain Wayne Rooney and Lallana – replaced Theo Walcott, Jesse Lingard and the injured Dele Alli.
Daniel Sturridge opened the scoring for England
Visiting captain Darren Fletcher had the game’s first effort, but miscued a half volley that Joe Hart collected comfortably.
Winger James Forrest then cut in from the left-flank and hit a low 20-yard drive straight at Hart in an encouraging start for Scotland.
Rooney was first to try and unlock Scotland’s well-drilled defence with a low through pass intended for Sterling, but centre-back Grant Hanley made a vital interception.
England soon grew into a game being played at an increasingly high tempo, epitomised by driving runs from Sterling, who drew a foul from Christophe Berra 25 yards from goal. Rooney though, saw his free-kick deflected wide.
Southgate’s men were now firmly on top and broke the deadlock on 24 minutes. Again it was Sterling at the heart of the action. His long-range effort was blocked by Hanley falling to Kyle Walker on the right side of the box, who picked out Sturridge at the near post and the Liverpool frontman headed his eighth England goal past Craig Gordon.
Scotland looked for an immediate reply and Leigh Griffiths’ first-time effort was blocked bravely by John Stones.
Hanley then found space eight yards from goal to meet Robert Snodgrass’s corner, but ballooned his header harmlessly over the crossbar.
Fletcher was next to try his luck shortly before half-time after neatly side-stepping Rooney, but blazed over the crossbar from 20 yards.
Scotland were quickest out the blocks after the interval and left-back Lee Wallace crossed for Forrest after a lung-busting run, but the Celtic man dragged his shot wide from the edge of the box.
Another smart break down the left-flank saw Snodgrass try his luck at the near post, but Stones was well-positioned to block.
The travelling support, doing their level best to match the vociferous home supporters, sensed a goal, but it was England who registered on 50 minutes.
Adam Lallana scored his first goal for England on home soil
Sturridge sent the ball wide to Sterling, who played in Danny Rose on the overlap. The Tottenham full-back floated a cross toward the penalty spot which Lallana met perfectly to guide his header beyond Gordon.
It was the Liverpool midfielder’s fifth goal for club and country this season.
Eleven minutes later England had a third headed goal of the evening when Cahill rose at the near post to turn in Rooney’s corner.
Scotland looked to have run out of puff and England went in search of a fourth.
Sterling could and should have got the goal his performance deserved with 20 minutes remaining, but diverted Henderson’s cross over the bar from two yards.
And the Manchester City winger then sent a low cross to the far post that just evaded substitute Jamie Vardy.
But England had already done more than enough and now have their tails up for the final international of the year when Spain visit Wembley Stadium on Tuesday.
England (4-2-3-1): 1 Joe Hart; 2 Kyle Walker, 5 Gary Cahill, 6 John Stones, 3 Danny Rose; 8 Jordan Henderson, 4 Eric Dier; 7 Raheem Sterling, 10 Wayne Rooney, 11 Adam Lallana; 9 Daniel Sturridge
Substitutes: 19 Jamie Vardy for Sturridge 74
Substitutes not used: 13 Tom Heaton, 23 Jordan Pickford, 12 Nathaniel Clyne, 14 Theo Walcott, 15 Phil Jagielka, 16 Ryan Bertrand, 17 Andros Townsend, 18 Harry Kane, 20 Marcus Rashford, 21 Jack Wilshere, 22 Jesse Lingard
Interim manager: Gareth Southgate
Goals: Daniel Sturridge 24, Adam Lallana 50, Gary Cahill 61
Yellow Cards: Gary Cahill 57
Red Cards: None
Scotland (4-2-3-1): 1 Craig Gordon; 2 Ikechi Anya, 5 Grant Hanley, 4 Christophe Berra, 3 Lee Wallace; 8 Scott Brown, 7 Darren Fletcher; 6 James Forrest, 10 Robert Snodgrass, 11 James Morrison; 9 Leigh Griffiths
Substitutes: 17 James McArthur for Morrison 66, 23 Callum Paterson for Anya 79, 20 Matt Ritchie for Snodgrass 82
Substitutes not used: 12 David Marshall, 21 Jack Hamilton, 13 Chris Martin, 14 Russell Martin, 15 Steven Naismith, 16 Steven Fletcher, 18 Barry Bannan, 19 Oliver Burke, 22 Stephen Kingsley
Head coach: Gordon Strachan
Yellow Cards: Leigh Griffiths 56
Red Cards: None
Referee: Cuneyt Cakir