Five of the hosts' seven goals at the Theatre of Dreams were made in North London, as Harry Kane also got in on the act with a brace alongside strikes from Marcus Rashford and Kalvin Phillips to seal a fourth win from four games in emphatic style.
Bringing back two of their Manchester City treble-winners in Kyle Walker and John Stones, as well as recalling Rashford to the final third on his regular stomping ground, it did not take long for England to take the game by the scruff of the neck.
However, North Macedonia held out admirably for the first 25 minutes and restricted the Three Lions to minimal clear-cut chances, although Stefan Ristovski was left bloodied for the cause after a nasty clash of heads with Kane.
In contrast, the England captain escaped with a protruding bump on his forehead, and he showed few ill-effects from that collision, scoring with his first touch in the penalty area in the 29th minute.
Red Devils teammates Luke Shaw and Rashford combined for the former to make a darting run into the box, and he subsequently cut back for Kane to calmly score for the sixth England game running.
Once the deadlock had been broken, the goals flowed for Gareth Southgate's men, who were in a particularly merciless mood at the Theatre of Dreams and doubled their advantage just nine minutes after Kane's opener.
A neat piece of link-up play between Trent Alexander-Arnold, Walker and Saka saw the Manchester City man find his Arsenal colleague in a pocket of space inside the box, and Saka proceeded to take a touch before letting fly with a thunderous strike into the roof of the net.
Having witnessed his fellow attackers Saka and Kane make the net bulge, Rashford soon wanted a slice of the action on home soil, and the Manchester United man put the game to bed on the stroke of half time.
Darko Velkovski was caught in possession by Kane next to his own corner flag, and the skipper fed Jordan Henderson to square for Rashford, who had a simple finish from inside the six-yard box.
In doing so, Rashford became the first Man United men's player to score for England at Old Trafford since David Beckham in 2001, and North Macedonia would not be granted any sort of reprieve following a welcome half-time break.
After combining for England's opener against Malta, the lethal Saka-Alexander-Arnold combination came to the fore again in the 47th minute, as the latter played an exquisite long ball over the top for Saka to chase, and the attacker controlled with his chest before unleashing a ferocious half-volley into the top corner.
Only four minutes later, the Arsenal protege would write more headlines with a maiden senior treble, charging through a disorganised North Macedonia defence to meet Kane's through ball and coolly finding the bottom corner to spark heart-warming celebrations; Saka's teammates and coaches on the bench looked on in the manner of proud family members.
Saka's haul made him the first Arsenal player to net an England hat-trick since Theo Walcott's terrific treble against Croatia in 2008, and the Three Lions' day of firsts continued in the 64th minute, as North Macedonia failed to deal with an inswinging Jack Grealish cross and were powerless to prevent Phillips from opening his England account with a simple tap-in.
The final whistle could not have come soon enough for North Macedonia, but their evening became even more humiliating when Egzon Bejtulai felled Stones inside the box, and Kane made no mistake from the spot to double his tally in the 73rd minute.
England's crushing win keeps them top of Group C with 12 points to their name, while Blagoja Milevski's side remain fourth, only ahead of a pointless Malta outfit.