The Chairboys took a surprise lead in the 22nd minute through Brandon Hanlan, however the Premier League champions responded quickly with three goals before half time from Kevin De Bruyne, Riyad Mahrez and Phil Foden.
After the break, Mahrez scored his second of the night, either side of strikes from Ferran Torres and Cole Palmer, with the latter netting his first senior goal for the club.
With several first-team players ruled out of the midweek clash due to injury, Pep Guardiola decided to hand six youngsters their senior debuts, with the Spaniard naming a back four who were all aged just 18.
Here, Sports Mole assess how each of Man City's youth players performed on a memorable night at the Etihad Stadium.
Conrad Egan-Riley
Local lad Conrad Egan-Riley - one of four City players on the pitch who were born in Manchester - was handed a start at right-back and played the full 90 minutes in Guardiola's side.
The defender, who has spent 10 years in City's Elite Development Squad, enjoyed a comfortable debut, dealing with every defensive duty that came his way and also looked positive going forward.
Egan-Riley re-gained possession on eight occasions during the match, more than any other City player.
Finley Burns
Finley Burns slotted in as the right-sided centre-back and was forced to battle hard with the 'beast' that is Adebayo Akinfenwa, though the 18-year-old was able to cope with the immense strength of his 39-year-old opponent.
The England Under-18 international was a powerful presence at the heart of the defence and made seven clearances in the 90 minutes, five more than any other City player.
Burns's astute performance displayed why the Citizens paid Southend United around £175,000 for his services back in 2017 when was aged just 13.
Luke Mbete
Luke Mbete, a left-footed central defender, partnered Burns at the back and started his first senior game just three days after his 18th birthday.
A tall, commanding presence at the heart of defence, Mbete was calm and composed on the ball and has a similar style to that of City legend Vincent Kompany.
The youngster, who has emerged as a key figure in the Under-23's set-up, enjoyed an excellent debut for the senior side, with several City supporters suggesting he is a rising star in the making.
Josh Wilson-Esbrand
Josh Wilson-Esbrand showcased a very promising shift at left-back and his efforts bombing down the flank played a big part in City's success going forward.
The 18-year-old provided the assist for the hosts' second goal of the night scored by Riyad Mahrez, skilfully running towards the byline before cutting it back for the Algerian to sweep into the net.
Wilson-Esbrand came off in the 72nd minute to rapturous applause and can be proud of his impressive display. The pacey youngster could potentially be the answer to City's well-established left-back problem in the not too distant future.
Romeo Lavia
At 17 years of age, the youngest debutant on the night, Romeo Lavia occupied the defensive midfield role just in front of the youthful back four, screening the space in front of them and delivering several balls forward to City's elite attackers in the final third.
Lavia, who was discovered by Guardiola in his homeland of Belgium while playing in the Kevin De Bruyne Cup back in 2018, has earned plenty of admiration since joining the youth academy and his talent was certainly on show for the senior side on Wednesday night.
With veteran midfielder Fernandinho turning 37 next year and with less than 12 months left on his contract, Lavia could be the tough-tackling technically-gifted midfielder that City call upon, given time.
James McAtee
James McAtee was brought on as a second-half substitute and although he plies his trade as an attacking midfielder for the youth team, the youngster agreed with Guardiola to play the final 20 minutes at left-back as he was so keen just to get on the pitch.
The 'Salford Silva' was still able to show glimpses of his talent out of position, though his qualities further forward are ones which have caught the eye among City's coaching staff.
McAtee has enjoyed a brilliant spell in front of goal for the youth team, scoring 11 goals and providing three assists in just seven games so far this season.
Cole Palmer
It was a memorable moment for every City youngster on Wednesday, though it was certainly a night to cherish for substitute Cole Palmer, who scored his first senior goal in the 88th minute to round off a comfortable victory for the hosts.
After picking up the ball from inside his own half, his Yaya Toure-esque run forward finished with a curling effort from 20 yards into the bottom left corner.
The 'Wythenshawe Wizard', who scored 13 goals and provided six assists for the youth team in Premier League 2 last season, has a bright future ahead of him and is one who Guardiola rates very highly.