A Greek tragedy unfolded for David Moyes in Athens as Arsenal loanee Joel Campbell scored a stunning goal to leave Manchester United on the brink of an early Champions League exit.
Campbell has not kicked a ball for the Gunners since signing in 2011, but he showed superb quality to score the second goal in a relatively straightforward 2-0 victory for Olympiacos.
Alejandro Dominguez's clever backheel put the Greeks ahead in the first half and from then on in Moyes' team rarely looked like being able to get back into the first leg of this last-16 tie.
Wayne Rooney and Nemanja Vidic had talked up United's chances of winning the Champions League in the build-up to the match, but it was easy to see why Moyes' side were 25-1 shots to land the trophy going into this match in the port suburb of the Greek capital.
Rooney worked tirelessly, as he always does, and Vidic put in a solid performance at the back.
But United's midfield, as it has done for much of this season, looked awfully pedestrian for the majority of the match, which was played out amid a booming atmosphere inside the Karaiskakis Stadium.
Olympiacos, who are bidding to make the last eight for only the second time, made a mockery of the away side's billing as favourites.
And without the cup-tied Juan Mata and Adnan Januzaj, who was overlooked, United looked toothless in attack.
With United 11 points adrift of the top four in the Premier League, winning the Champions League may be the best way to get back into the competition next year, but they will have to win by three clear goals in the second leg on March 19 to make it through to the quarter-finals after this latest sub-par performance.
CARRICK CRESTFALLEN AFTER DEFEAT
Midfielder Michael Carrick admitted Manchester United were left with a tough task to stay alive in the Champions League after a shock 2-0 first-leg defeat at Olympiacos.
Alejandro Dominguez and Joel Campbell scored in either half to complete a miserable night for David Moyes' under-pressure side.
Carrick put on a brave face afterwards, suggesting United can still progress when the last-16 tie moves to Manchester, but admitted the Greek side were in "a great position".
"It's hugely disappointing but we feel like we're still in with a chance going back to Old Trafford," he told Sky Sports 2.
"Obviously it's not going to be easy.
"We've lost a game we came here hoping to win and haven't done that.
"We're not out of tie by all means, but it's not ideal."
Asked what went wrong, Carrick added: "I'm not sure. We had good possesion in the first half. We had control of the game without penetrating their line, but at same time they weren't causuing us any problems.
"The goals came from nothing, but it obviously puts them in a great position.
"We didn't start the second half very well. A bit sloppy really."
Robin van Persie missed a glorious late chance to snatch an away goal, but Carrick did not want to aportion blame.
"You can't blame Robin; he's created his chance and nearly scored," he said.
"As players we have to stand up and take it on the chin.
"That's the business we're in. You take the good times and the bad times. We have to keep trying.
"You're looking for me to blame someone. As players we haven't been getting good results and as a club that's everyone involved. That's how we are judged."
MAN UTD PLAYER RATINGS
DAVID DE GEA: Wrong-footed for first goal. Could do little about the second. 5/10.
CHRIS SMALLING: Slipped on a number of occasions. Was supposed to offer more security than Rafael but he was casual on the ball and lost the ability to tackle. 4.
RIO FERDINAND: Lack of pace uncovered again. 5.
NEMANJA VIDIC: The only United defender to stand up. Put in a couple of crucial challenges on his 50th Champions League appearance. 7.
PATRICE EVRA: Booked for early hand ball. Sloppy error in run-up to Olympiacos' first. 5.
TOM CLEVERLEY: Another game where the England midfielder went AWOL. Did well to last an hour before being hooked. 4.
MICHAEL CARRICK: Failed to dictate the tempo as Moyes would have liked and offered little defensive security. 5.
ASHLEY YOUNG: Puzzling choice ahead of Adnan Januzaj. Barely featured. 4.
WAYNE ROONEY: Marked out of the game. Spent as much time in his own half as he did in the opposition's. 5.
ANTONIO VALENCIA: Couple of telling tackles, but did nothing to help the United attack. 4.
ROBIN VAN PERSIE: A shadow of the player who went into the match in form. 5.
SHINJI KAGAWA on for Valencia (61mins). Provided energy but nothing else. 5.
DANNY WELBECK on for Cleverley (61mins). Exactly the same as Kagawa. 5.
UNITED'S SEASON OF MISERY
Manchester United suffered another painful defeat as a 2-0 loss to Olympiacos in Greece put their Champions League hopes in peril.
Manager David Moyes will hope his team can turn around the tie in the second leg at Old Trafford, but it was another grim night for the former Everton boss and the team he inherited as English champions from Sir Alex Ferguson.
Here, Press Association Sport picks out the lowest points from the Scot's short reign so far.
September 1 - Suffer first defeat as Daniel Sturridge gives Liverpool victory at Anfield. Wayne Rooney misses the game with a nasty head wound after being kicked in the head by Phil Jones in training.
September 22 - Hammered 4-1 at Manchester City. This time Robin van Persie is absent with a thigh injury.
September 28 - Suffer first in a series of shock defeats, 2-1 at home to West Brom, ending the Baggies' 35-year wait for an Old Trafford triumph.
October 19 - Concede last-minute Adam Lallana equaliser against Southampton at Old Trafford.
December 4 - Bryan Oviedo scores four minutes from time as Everton end their 21-year wait for an away win over United.
December 6 - Rio Ferdinand criticises Moyes' policy of leaving it late to pick his teams, claiming on BT Sport: "It turns you into a madman."
December 7 - Yohan Cabaye gets the only goal as Newcastle win at Old Trafford for the first time since 1972.
December 10 - Van Persie suffers thigh injury taking a corner against Shakhtar Donetsk, and is ruled out for seven weeks.
January 1 - Rooney plays in the defeat by Tottenham but is then ruled out for four weeks with a groin injury.
January 5 - Swansea win at Old Trafford for the first time as Wilfried Bony's late goal sends United out of the FA Cup at the third-round stage for the second time in 30 years.
January 7 - Defeat in Capital One Cup semi-final first leg at Sunderland means a third straight loss for the first time since May 2001.
January 19 - Skipper Vidic is sent off as United crash to defeat at Chelsea.
January 22 - United beat Sunderland 2-1 in the Capital One Cup semi-final return leg thanks to Javier Hernandez's last-gasp effort in extra time, but come off worst in an awful penalty shoot-out, with only Darren Fletcher scoring from their five kicks.
February 1 - Stoke end their long wait for a win against United. Charlie Adam's double gives them their first since 1984.
February 7 - Vidic confirms he will leave at the end of the season.
February 9 - United come from behind to lead bottom side Fulham at Old Trafford, but Darren Bent's stoppage-time equaliser settles a 2-2 draw to deny the hosts all three points. Moyes describes the result as being "as bad as it gets".
February 25 - It proves gruesome in Greece for United in the Champions League last 16 as a poor performance sees the Red Devils beaten 2-0 by Olympiacos in Piraeus.