Kaan Bennett opened the scoring for the visitors with less than two minutes on the clock, linking up well with skipper Gene Kennedy on the edge of Leeds' penalty area, before slotting beyond Darryl Ombang.
Leeds took less than a minute to restore parity, however, levelling through first-team fringe player Darko Gyabi. Keenan Carole's neat touch and surging run down the right unlocked space in the middle for Gyabi to penetrate as he met Carole's low cross, sweeping in the equaliser.
Starting alongside fellow fringe member of Daniel Farke's squad Lewis Bate, Gyabi was deployed in attacking midfield during the first half, while Bate occupied his more reserved, and fairly typical, central midfield role. That did not prevent the ex-Chelsea youngster finding the back of the net with a rasping effort from range shortly after Gyabi's equaliser.
Carole again proved the architect, cutting back to Bate who upon first impressions was not in an immediately dangerous position. Driving forwards with the ball, Bate lined up a shot from 25 yards, striking the underside of the bar and registering his first goal of the season as the ball bounced up and into the roof of the net.
Colchester drew level minutes later courtesy of a heavy deflection on Chay Cooper's shot from the edge of Leeds' 18-yard area.
Skubala's roll of the dice at the break saw the more experienced pair of Sean McGurk and Charlie Allen introduced, along with Max McFadden, all of whom brought fresh legs, technical ability and dynamism to the Leeds attack.
Shortly before the 70-minute mark, Allen and McGurk combined, via the frame of the goal to put Leeds in front once more. The ex-Wigan youngster netted his four goal in five games this season with a composed finish after Allen's low effort had ricocheted back off the woodwork.
Leeds' remaining PL Cup group stage opponents are Chelsea and Luton Town. Skubala's youngsters have now won four of their five matches across all competitions this season.
Leeds XI: Ombang (GK), Moore, Spencer, Debayo, Ferguson (Godden 83’), Bate, Coleman (Allen 46'), Gyabi, Douglas (McFadden 46'), Carole (McGurk 46'), Thomas
Unused subs: Christy (GK)
Final score: Leeds United U21s 3-2 Colchester United U21s