The young Reds fell behind to Jack Roles’ strike early in the second half and could not find a way back into the game with 10 men after Adam Lallana was shown a red card.
George Johnston was dismissed for a second bookable offence in the closing moments, too, on a night that Neil Critchley’s side will want to forget.
The U23s were boosted by the availability of four first-team players in Danny Ings, Lallana, Dominic Solanke and Ben Woodburn – all of whom started at the home of Stevenage FC.
Chances were created constantly in the first half and Solanke might have put the Reds ahead from either of two quick-fire openings forged by strike partner Ings on four minutes.
First, the latter teed his younger colleague up with a backheel into the area only for Jonathan Dinzeyi to prevent the shot, before the No.10 failed to convert from a subsequent cross.
In riposte, Dylan Duncan flashed an effort wide to the left after a nimble turn 20 yards from goal, before Ings came within inches of breaking the deadlock.
Woodburn, on the left hand side, picked out the forward with a precise knock into the area and the Englishman’s chest-and-shot was agonisingly close to perfect – but just off target to the right.
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Another lofted delivery from that flank by Woodburn had Solanke and Ings queuing up to pounce. But both the former’s header and the latter’s follow-up were saved by Luke O’Reilly.
And Spurs finished the half the stronger.
Kazaiah Sterling clipped the ball wide having broken free into a one-on-one situation, Keanan Bennetts fired a clear-cut chance over the crossbar from 10 yards, and Kamil Grabara clawed out a Roles drive on the stretch.
The end-to-end nature of the tie continued after the interval. Jaden Brown blocked a weak Adam Lewis hit from Lallana’s nod back, while Sterling again squandered a fine opportunity with a short-range attempt too close to the goalkeeper.
But Tottenham finally produced the breakthrough on 55 minutes.
A long ball caught Liverpool short of numbers and Spurs took full advantage, attacking at speed and fashioning space for Roles to force a bouncing finish past the touch of Grabara.
The Reds’ hopes of restoring parity were dented by Lallana’s red card shortly after the hour mark. The midfielder reacted angrily to a headed challenge with George Marsh and was immediately sent off.
Critchley’s charges continued to push for an unlikely leveller but nothing materialised and Johnston’s late dismissal compounded a frustrating evening for the visitors.
Liverpool U23s: Grabara, Masterson, Lewis, Johnston, Gallacher, Kane, Dhanda (Millar, 72), Lallana, Ings, Solanke, Woodburn.
Unused substitutes: Camacho, Kelleher, Gomes, N. Williams.