Marcus Rashford and substitute Kalvin Phillips also scored.
Saka achieved his first career hat trick in style and manager Gareth Southgate later revealed the forward carried an injury into the game.
“He’s had a slightly sore Achilles and it’s another one where it would have been easy to pull out of the camp and miss out on a night like this that I’m sure will live with him forever,” Southgate said.
Saka smashed an unstoppable effort into the top corner at the near post in the first half. Two minutes after the break came a moment of solo brilliance when he hit a dipping shot beyond North Macedonia goalkeeper Stole Dimitrievski from the edge of the area. Four minutes later, he burst through on goal and delivered a cool finish.
“It’s a feeling I can’t put into words. I’m so happy,” Saka said. “It’s been a really long season. It’s the end of the season now. I couldn’t have ended it in a better way.”
Fresh from beating Malta 4-0 on Friday, Southgate’s team produced an even more emphatic performance at the home of Manchester United.
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Kane’s strike in the 29th minute got England going after he was set up by Rashford and Luke Shaw.
Saka’s first doubled the lead in the 38th from a Kyle Walker pass from the right.
Rashford made it 3-0 in the 45th after Jordan Henderson’s assist from the left.
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A quickfire double after the break saw Saka complete his hat trick with assists from Trent Alexander-Arnold and Kane.
Phillips converted from close range in the 64th, five minutes after coming on as a substitute, and Kane converted a penalty in the 73rd after John Stones was brought down by Egzon Bejtulai in the box.
It is just over 12 months since Southgate and England were booed off the field by fans following a 4-0 home loss to Hungary in the Nations League.
Following elimination in the World Cup quarterfinals in Qatar, England is rekindling optimism that Euro 2024 could deliver a first trophy since the 1966 World Cup.
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“Post World Cup I think we’ve hit a sweet spot where there is a hunger to go further than we’ve been and a desire to keep pushing forward,” Southgate said. “That’s a good place to be.”
