Southampton's surprise defeat by Cardiff on Saturday, in a game Saints dominated at times, came as a major blow after three successive home wins had them among the four-way battle for automatic promotion.
With Stuart Armstrong also leaving that game on a stretcher, and unlikely to play for Saints again this season, the cost of that loss was high.
The absence of the Scotland international forced one of three changes, while the Foxes made two themselves with Ricardo Pereira and James Justin coming into the backline.
After 25 minutes of relentless pressure, a threaded pass from Kiernan Dewsbury-Hall unpicked Saints’ resistance and allowed Fatawu to get in behind Kyle Walker-Peters. The 20-year-old then beat goalkeeper Alex McCarthy with a composed side-footed finish into the bottom corner.
As Fatawu wheeled away and performed a backflip in celebration, Saints reacted angrily as the flag stayed down for offside, and they also felt Wout Faes had escaped punishment for a tackle on Che Adams that won back possession and started the goalscoring move.
It was not until the second half that Saints put Leicester under any meaningful pressure, with Russell Martin’s side emerging from the break with a sense of urgency and tempo that was previously lacking.
Even then, they could not break Leicester down and finished the game without registering a shot on target.
Ndidi's header to double Leicester's advantage triggered a merciless final 30 minutes that had Foxes fans in the stands at King Power Stadium in ecstasy.
Fatawu’s curled finish from outside the box to make it three was the pick of the goals, and his pass to find Vardy soon after was the pick of the assists before the 37-year-old returned the favour at the end of a fast-flowing counter-attack to make it 5-0.