Kane put the home team ahead in the 14th minute with his 100th goal in club football, with 84 of them coming for Spurs.
He added another 18 minutes later, volleying in from a corner and completed his third treble in six weeks with a deflected shot. Dele Alli made it 4-0 before halftime from Kane's cross.
It was a stunning individual performance by the 23-year-old Londoner, who had previously scored hat-tricks against West Bromwich Albion on Jan. 14 and then at Fulham in the FA Cup last Sunday.
The team's display also justified manager Mauricio Pochettino's decision to field an unchanged side despite Spurs having less than 72 hours' rest after going out of the Europa League against Gent at Wembley on Thursday.
Mid-table Stoke, in contrast, derived no benefit from having had 15 days without a game and were outplayed throughout.
Spurs pressed from the start with some neat close-passing and Kane opened the scoring with an opportunistic effort as the ball ran to him off a defender.
Soon after Jan Vertonghen had struck the bar with a fierce drive, Christian Eriksen spotted Kane unmarked at a corner and picked him out for a perfect low left-footed volley.
Eriksen next teed up a free kick for the striker, whose shot went in off a defender. The goal was credited to Kane, who then did brilliantly on the right flank just before halftime, setting up Alli to score.
Stoke, who were no doubt given a talking to at the interval by manager Mark Hughes, livened up in the second half but Kane was only denied his fourth goal by a fine low save from Lee Grant.
"We wanted to come out and get back to winning ways," Kane told Sky Sports.
"It was exactly what we need. I just tried to get my shots off and if you don't shoot, you don't score."
(Reporting by Steve Tongue; Editing by Toby Davis)
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