Mollie Green, Lauren James and Kirsty Hanson gave the home side a three-goal lead before the break as City's women endured a tough afternoon in Manchester.
After the interval, Ella Toone added a fourth and, while Libby Smith did get one back for City, Jessica Sigsworth struck a brace to confirm her side's dominance.
One particular landmark for Leicester to celebrate, however, came as Northern Ireland international Natt Johnson marked her 100th appearance for the women's team.
Next up, the Foxes welcome Sheffield United to Farley Way Stadium in Quorn as they go in search of a first victory in six matches.
They welcome the Blades to Leicestershire on Sunday 31 March for a 2pm GMT kick-off. City are currently sixth in the FA Women's Championship standings, with 20 points.
City: Lambourne, Franklin-Fraiture, Jackson, Nymoen, Morgan (c), Johnson, Axten (Domingo 71'), Ayisi (Dugmore 60'), James, N. Johnson, Smith (Worts 71')
Subs not used: Clarke, Brown, L. Johnson, Moncaster
Goal: Smith 59'
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