Manchester United defeated Barcelona 2-1 after coming from behind. In UEFA Europa League, knock out a tie at Old Trafford on Thursday night.
Robert Lewandoski gave Barcelona an early lead at the Theatre of Dreams after converting a penalty past David De Gea.
The goal by the Poland striker was his first-ever goal on his first Old Trafford visit and his first goal against Manchester United.
However, the La Liga leaders were once more defeated by the transition to the European stage as Fred tied the score early in the second period before Antony produced his most memorable performance since moving to Manchester from Ajax.
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The fact that two of the continent's heavyweights were squaring off at this point in the second-tier European tournament was proof that both had recently encountered more difficult circumstances.
But, while the Red Devils continue to pursue championships on four fronts, United are riding the crest of a wave in Erik ten Hag's inaugural season as manager.
When United plays Newcastle in the League Cup final on Sunday, they might finally win a trophy after a six-year absence.
But they didn't hold back to claim their most significant European victory since shocking Paris Saint-Germain in the Champions League round of 16 in 2019.
Although United had to come from behind for the second time in the match to win, they are now unbeaten at Old Trafford in 18 games dating back to September.
Within three minutes, Bruno Fernandes had a golden opportunity to give the home team the lead, but his angled shot but Marc-Andre ter Stegen's foot stopped the picture using his foot.
Since being eliminated from the Champions League group stage by Bayern Munich and Inter Milan in October, Barcelona has gone unbeaten in all competitions.
Even the initial goal presented itself as a gift that the visitors should have capitalized on.
After Alejandro Balde carelessly attempted to be caught by Fernandes, French referee Clement Turpin incensed Old Trafford by indicating to the area.
David De Gea stopped Lewandowski's penalty, but near the hour mark, the ball rebounded off the post and into the goal.
Due to an injury and a suspension, Barca was without Pedri and Gavi's poise and ingenuity in the middle of the field.
Yet, Xavi's team continued to dominate the rest of the first half without ever appearing to be in danger of extending their lead.
During halftime, Ten Hag replied by substituting Antony for the ineffective Wout Weghorst, and within two minutes, the substitutes gave Erik Ten Hag a reason to play them.
In his usual central midfield position again, Fernandes found Fred, who blasted low past, Ter Stegen.
Jules Kounde's header from close range required a fantastic save from De Gea to keep the momentum from shifting back towards the Catalan giants.
Since being reunited with Ten Hag after an £86 million transfer from Ajax, Antony has played the flatter-to-deceive card.
But, 17 minutes from the end, the Brazilian gave the winner a performance deserving of the price tag.
The ball set up perfectly for Antony to curl past Ter Stegen's extended arm after Alejandro Garnacho and Fred blocked their attempts.