Manchester United's Champions League dreams are over after being rocked by Sevilla, with substitute Wissam Ben Yedder's brace securing a famous win against Jose Mourinho's lacklustre side.
Last month David De Gea saved the Red Devils' blushes as they escaped Andalusia with a goalless draw, but Vincenzo Montella's men did not allow another undercooked display to go unpunished.
An abject United performance got the outcome it deserved as Sevilla kicked on after a solid first-half display, with Ben Yedder coming off the bench to secure a 2-1 win and render Romelu Lukaku's late goal pointless as the Spaniards progressed from the last-16 at the fourth time of asking.
The celebrations on the pitch were as wild as they were in the away end at full-time, while United were jeered off the field as the biggest week of their season was thrown off kilter.
Former United captain Rio Ferdinand questioned the players' attitudes.
"They just played nervous and cautious from the beginning," he said on BT Sport. "In these games you've got to take the game by the scruff of the neck. That takes personality. It takes characters to do that in this stadium. You've got to give the fans something to chant about. This stadium tonight was quiet, and that's down to the players."
He continued: "The attitude just seemed off, lethargic."
Mourinho's side showed none of the intensity displayed in the weekend win against rivals Liverpool, with Marouane Fellaini mustering the only noteworthy shot in a first half that the visitors edged.
Worse still, there was little response from the hosts in the second period.
Ben Yedder came off the bench to add another attacking dimension in the 72nd minute and within six minutes had ended the tie, following a fine low strike with an effort that De Gea could not prevent from crossing the line.
Lukaku reduced the deficit with six minutes remaining, but Sevilla had done enough to progress and leave United's hopes of silverware resting on the FA Cup ahead of Saturday's quarter-final against Brighton.
Old Trafford was half empty by the full-time whistle came, with those remaining booing a performance that started badly and only got worse.
Lukaku's early threat and a deflected Marcus Rashford free-kick followed by a fragmented first-half display, with Joaquin Correa losing marker Nemanja Matic to head just over.
Eric Bailly blocked a Franco Vazquez snapshot before inexplicably gifting the visitors possession, only to see Luis Muriel fire over - a player who drilled wide as a pocket of United fans started to chant "attack, attack, attack".
Fellaini, making his first start since November, forced Sergio Rico into a save as the hosts threatened to take an undeserved lead into a break they returned from sloppily.
Just three minutes after the restart Sevilla broke and Correa was inexplicably allowed to run free into the box. He collected Pablo Sarabia's cross and cut past Rashford, only to be denied by a thumping Bailly tackle.
Jesse Lingard forced a fine one-handed save from Rico and Rashford fizzed across the face of goal when United unleashed their first threats, but Correa got away an attempt that bobbled wide as tension began to rise.
Muriel was just unable to bundle home a Sarabia cross and Fellaini blazed off target - the Belgian's last contribution before Mourinho turned to Paul Pogba.
The club-record signing came close with a curling 25-yard attempt after Lukaku and Rashford tried their luck, but Sevilla continued to threaten and went ahead in the 74th minute.
Just 87 seconds after coming off the bench, Ben Yedder was put through by Sarabia and sent a right-footed strike past De Gea.
United wilted rather than rallied, with Sevilla securing progress in the 78th minute.
Ever Banega's corner was flicked on for Ben Yedder to get away a header that De Gea tipped onto the bar, only for it to agonisingly curl over the line.
United belatedly increased the intensity, peppering the Sevilla box in the hope of an unlikely turnaround.
Lukaku hooked wide and then fired in a Rashford corner in the 84th minute, with Martial having a cross-shot blocked before Rashford headed wide.
De Gea denied Ben Yedder a hat-trick in stoppage time, but there was no stopping Sevilla.
Joining Sevilla in Friday's quarter final draw will be Roma.
Edin Dzeko's goal seven minutes into the second half saw them beat Shakhtar Donetsk 1-0 at the Stadio Olimpico to go through on away goals.