Arsenal turned the form book upside down and gave manager Arsene Wenger much-needed respite with a shock 2-0 win away to AC Milan in the Europa League on Thursday.
The London side, who had lost their last four games in all competitions and were facing a Milan team unbeaten in 13 matches, stunned the San Siro with first-half goals from Henrikh Mkhitaryan and Aaron Ramsey in the round of 16 first leg.
Lazio completed an unhappy night for Italian clubs when they were held 2-2 at home by Dynamo Kiev while Bundesliga side Borussia Dortmund suffered a shock 2-1 home defeat by Austrian champions Salzburg.
Twice former champions Atletico Madrid eased past Lokomotiv Moscow 3-0 as all three Russian clubs lost.
With Arsenal sixth in the Premier League and Milan seventh in Serie A, the match was played in very different circumstances to their last clash six years ago.
On that occasion, both teams were Champions League regulars and met in the round of 16 of Europe's top club competition.
Arsenal went ahead after 15 minutes after Mesut Ozil found Mkhitaryan on the left side of the penalty area and the Armenian scored his first goal for the London club with a deflected shot.
Having refound their confidence, Arsenal played some flowing football as they repeatedly caught Milan on the break, leaving the Serie A side's coach Gennaro Gattuso red-faced with anger on the touchline.
Mkhitaryan rifled a shot against the crossbar before Ozil produced another inspired pass to send Ramsey clear and he rounded goalkeeper Gianluigi Donnarumma to add the second in the 45th minute.
Milan were more purposeful in the second half but Arsenal held out comfortably with a resilience missing from their recent performances.
“We were not in a position to take risks, but we could not be too cautious as you lose fluidity," Wenger said. "We defended with resilience until the end."
Valon Berisha scored twice early in the second half, the first from a penalty, as Salzburg stunned Dortmund, who replied through Andre Schuerrle.
Saul Niguez set Diego Simeone's Atletico on their way against Lokomotiv Moscow with a rising 25-metre shot before Diego Costa and Koke struck to complete an easy win for the Spanish side in Madrid.
Olympique Lyonnais defied freezing conditions to win 1-0 at CSKA Moscow thanks to Marcelo's second-half strike and RB Leipzig beat Zenit St Petersburg 2-1 after second-half goals from Bruma and Timo Werner.
However, Domenico Criscito brought Zenit right back into the tie when he scored from a free kick in the 86th minute.
There were four second-half goals in less than half an hour in Rome where Viktor Tsigankov gave Kiev the lead in the 52nd minute before Ciro Immobile, with his 33rd goal of the season, and Felipe Anderson turned the game around for the Serie A side.
However, Dynamo levelled in the 79th minute with a superb effort from Junior Moraes who collected the ball on the edge of the area, turned and curled his shot past Thomas Strakosha.
Lucas Ocampos scored twice, including the Europa League's fastest goal of the season after 36 seconds, to set Olympique Marseille on the way to a 3-1 win over Athletic Bilbao.
Dimitri Payet netted Marseille's other goal, his first in Europe since 2009 when he was on target for St Etienne, and 37-year-old forward Aritz Aduriz replied with a penalty for the visitors.
Fredy Montero scored twice either side of halftime to give Sporting, Portugal's last European survivors, a 2-0 win at home to Viktoria Plzen in the other game.
Last 16, first legs
AC Milan (ITA) 0 Arsenal (ENG) 2
(Mkhitaryan 15, Ramsey 45+4)
Atletico Madrid (ESP) 3
(Niguez 22, Costa 47, Koke 90) Lokomotiv Moscow (RUS) 0
CSKA Moscow (RUS) 0 Lyon (FRA) 1
Borussia Dortmund (GER) 1
(Schurrle 62) Salzburg (AUT) 2
(Berisha 49-pen, 56)
Lazio (ITA) 2
(Immobile 54, Anderson 62) Dynamo Kiev (UKR) 2
(Tsygankov 52, Moraes 79)
Marseille (FRA) 3
(Ocampos 1, 57, Payet 14) Athletic Bilbao (ESP) 1
RB Leipzig (GER) 2
(Bruma 56, Werner 77) Zenit St Petersburg (RUS) 1
Sporting Lisbon (POR) 2
(Montero 45+1, 49) Viktoria Plzen (CZE) 0
-- Second legs to be played on March 15