Manchester United were beaten 4-1 by Como at the Stadio Giuseppe Sinigaglia, a result that heaps further pressure on manager Michael Carrick.
Argentina playmaker Nico Paz scored after 118 seconds, set up Tasos Douvikas for the second on 49 minutes and added his own second on 57.
Jacobo Ramon headed in a fourth on 76 minutes, while Joshua Zirkzee, who beat the offside trap to meet a cross from Amad Diallo, scored a consolation in stoppage time.
The early goal made United the first English side to concede inside the first two minutes of consecutive major European matches.
Eight days earlier they had let in after the first minute against Atletico Madrid.
Como led 1-0 at half-time and the margin could have been wider, with United at one stage threatened with equalling their record European defeat, a 5-0 loss to Sporting in 1964.
Carrick made changes at the interval, withdrawing Matheus Cunha and Andrey Santos, who cost a combined £110m, for Diallo and Carlos Baleba.
Captain Bruno Fernandes made way for Zirkzee on 67 minutes, as defender Matthijs de Ligt, playing on his return from 11 months out, was replaced by Harry Amass on 79.
Goalkeeper Senne Lammens made a near-post save on a slippery surface and was rated the visitors’ best performer, though he could do little about the opener or the third.
Noussair Mazraoui struggled most, losing his footing under pressure and being beaten by Como’s Alberto Moreno da Cunha.
When United last won the Champions League in 2008, Como were in Serie D.