The Foxes’ first league outing in 16 days, following their narrow 2-1 loss at Derby County, saw them face the Citizens in Manchester.
In the opening stages, Ben Nelson did well to block an effort from Liam Delap, who this season made his Premier League debut under Pep Guardiola.
Then, Tommy Doyle saw an effort turned away before Jakub Stolarczyk did well to deny Cole Palmer as the hosts continued to press for an opener.
That goal arrived on 37 minutes, when Felix Nmecha headed home Palmer’s cross, before the latter made it 2-0 shortly after.
Stolarczyk was called into action again after the interval, blocking Delap’s strike, but City were reduced to 10 men early on in the second period when Ali Reghba was shown a red card for a late tackle on Nmecha.
Enzo Maresca’s outfit set about extending their advantage as Delap hit the bar and Adrian Bernabe was denied on the follow-up.
However, further efforts from Nmecha and Palmer secured a 4-0 success for the Manchester outfit, as the Foxes returned to Leicester empty handed.
The Foxes next travel to Brighton & Hove Albion in Premier League 2 on Friday 23 October (7pm BST kick-off) at the Amex Elite Football Performance Centre.