The midfielder returned to action off the bench against Espanyol last weekend and this represented a first start since his serious knee injury in January.
He played his part in an outstanding performance where the team's movement and precise passing was just too much for the visitors.
Tom Carroll was pivotal to it all. He pulled the strings in the midfield three alongside Sandro and Nabil Bentaleb, scored the first goal, set-up two of Kane's three goals and began the move for the fifth.
It was 5-1 after 64 minutes, City reduced arrears to 5-3 before Shaq Coulthirst completed the scoring with the last kick of the game.
It took only three minutes for Carroll to open the scoring, running onto a loose ball and placing a low shot, no more than a sidefoot, beyond Angus Gunn into the corner.
Yago Falque shot over, Kabe headed straight at Gunn and Dominic Ball headed over before City's first serious chance, a quick break and Jordy Hiwula fired wide from 20 yards.
It was only a brief respite though as Sandro powered a header just wide from Carroll's cross and Kane angled Zeki Fryers' low centre the wrong side of the post.
The second goal arrived on 35 minutes as Carroll released Kane, who beat the outrushing Gunn to convert, taking a whack in the process.
Outgunned in the first half, City found a way back just before the break as Marcos Lopes won possession and burst through centrally before firing home from the edge of the area.
Into the second half and Carroll kick-started the move for the third goal on 53 minutes with a wonderful crossfield pass to Andros Townsend. There was no stopping the winger, who darted to the byline before squaring for Falque to finish from close range.
Carroll claimed another assist for 4-1 two minutes later, this time clipping a ball over the top fo Kane, who controlled superbly before arrowing the ball into the corner.
The fifth goal and Kane's hat-trick was a carbon copy of the third. This time, Sandro played the crossfield pass to Townsend and his cross was diverted into the top corner by Kane from 10 yards.
City substitutes Harry Bunn and George Glendon provided two fine finishes after 70 and 79 minutes before Coulthirst, also off the bench, had the final word in the 92nd minute, there when it mattered to tap home after Bentaleb's header came back off the crossbar.
Spurs U21s: Archer; A McQueen (Coulthirst, 78), Ball, Stewart, Fryers; Bentaleb, Carroll, Sandro (Dombaxe, 67); Falque, Kane, Townsend. Unused subs: Miles, Gallifuoco.
Manchester City: Gunn, Drury, Leigh, Deneyer, Bossaerts, Evans, Bytyqi, Hutton, Hiwula (Bunn, 63), Lopes (Glendon, 53), Ntcham. Unused subs: Lawlor, Huws, Plummer.
Goals: Spurs - Carroll (3), Kane (35, 55, 64), Falque (53), Coulthirst (90+2). City - Lopes (44), Bunn (70), Glendon (79).