Kyle Walker and John Stones both started in a back three, while Gareth Southgate opted for Raheem Sterling and Phil Foden on either flank before Jack Grealish was introduced as a second half substitute.
Sterling laid on the England skipper for his second and the Three Lions’ fourth after the half-hour, as Kane overtook Wayne Rooney as his country’s highest-ever competitive goalscorer.
And the Tottenham man’s treble was completed on the stroke of half-time as he volleyed home Foden’s inch-perfect corner in spectacular fashion at the far post.
It rounded off a devastating first half performance from Gareth Southgate’s side, which had already seen the hosts go three goals ahead inside 28 minutes.
Harry Maguire headed home England’s first early on from a Reece James free kick, before Kane nodded in from close-range after clever play from Jordan Henderson and Foden down the left.
Kane returned the favour before the half-hour for Henderson’s second international goal, before bumping his own personal Three Lions’ tally up to 44 before the break.
While no further goals would follow in the second 45, the damage had already been done by Gareth Southgate’s men, who now need to avoid defeat against San Marino on Monday to guarantee their spot at the 2022 Qatar World Cup.
Grealish was handed his 18th international appearance after shaking off an illness earlier this week when he replaced Foden after the hour and looked his creative, energetic self from the left flank.
And Raheem Sterling was given a well-earned rest soon after, making way for Emile Smith-Rowe with 15 to play as the Arsenal man made his senior international bow.
The victory means England are guaranteed at least a play-off spot in European Qualifying, and also remain top of Group I.
Gareth Southgate's side remain three points ahead of second-placed Poland, the only side who can still catch them, after they beat Andorra 4-1 in Andorra la Vella.