Following a three game unbeaten run last month, a defeat by regular title contenders Chelsea early in October was followed by a two-week break for the young Foxes.
Back in action at Southampton's Staplewood training ground, Kasey McAteer and Adam Leathers returned to the starting line-up, replacing Will Russ and Sidnei Tavares.
However, the Saints were ahead inside 15 minutes as Jayden Smith collected the ball and finished well past Oliver Bosworth after some impressive work by Kazeem Olaigbe.
The home side's advantage was doubled through Jack Turner, who benefited from an incisive forward pass from James Morris cross for his third goal in two games.
While City went in at the break two goals down, they showed an incredible resilience to haul themselves back into the contest and eventually leave with all three points.
A neat one-two involving Dennis Gyamfi allowed McAteer to net for the young Foxes on 54 minutes before, within minutes, Leicester were level through Connor Barrett's deflected effort.
The visitors made it 3-2 with just 15 minutes to go, meanwhile, as Terell Pennant surged down the flank and located McAteer in space to pick his spot beyond Saints 'keeper Matt Hall.
Going into next Saturday's visit of Brighton & Hove Albion to Belvoir Drive (11am BST kick-off), City sit in fifth place in the U18 Premier League South standings with 11 points.
The details...
City: Bosworth (c); Flynn, Gyamfi, Sams, Barrett; Loughlin (Tavares 76'), McAteer, Leathers; Arlott-John (Russ 76'), Pennant, Fitzhugh
Subs not used: Doherty, Aisthorpe, Murch
Goals: McAteer 54', 75', Barrett 56'