Tottenham were without 11 players for their cup defeat at Aston Villa but the roles were reversed for this fixture with Ange Postecoglou boosted by the return of Guglielmo Vicario and Maddison, while United lost Manuel Ugarte, Kobbie Mainoo and Amad Diallo to injury over the weekend.
Maddison celebrated with a shush to the camera after midweek criticism from ex-Man United captain Roy Keane and this first home league win for Tottenham since November 3 moved the hosts' up to 12th in the table.
Spurs fans had protested against chairman Daniel Levy and majority owners ENIC earlier in the day, but come full-time it was injury-hit United and boss Ruben Amorim who were left to reflect on where to go next following another league defeat.
James Maddison's 13th-minute goal secured Tottenham a much-needed 1-0 win over Manchester United in the battle of the Premier League's crisis clubs.
The two teams started the day closer to the relegation zone than the top-four and it was Spurs who gained three points following an early effort by the fit-again Maddison.
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