Liverpool endured a humbling night after Atalanta left Anfield with a 3-0 victory that places the Serie A side on the brink of qualifying for the Europa League semi-finals.
Former West Ham striker Gianluca Scamacca struck in each half, the second goal made possible by a superb pass from Charles De Ketelaere, before Mario Pasalic added the third in the 84th minute.
Jurgen Klopp’s Premier League title challengers were completely outplayed by opponents positioned sixth in their domestic league and as a result have a mountain to climb in the second leg of their last eight tie.
West Ham were breached by two late goals as they slipped to a 2-0 defeat in their first leg at Bayer Leverkusen.
The Hammers had defended heroically for 83 minutes before goalkeeper Lukasz Fabianski was finally beaten by substitute Jonas Hoffman.
The second arrived in stoppage time when a second sub, Victor Boniface, headed home Hofmann’s cross to leave West Ham’s hopes of a third consecutive European semi-final looking slim.
Benfica took a step towards the reaching the last four after dispatching Marseille 2-1 in Lisbon through goals by Rafa Silva and Angel Di Maria.
The Portuguese champions were on target either side of the interval with David Neres involved in both strikes before Pierre-Emerick Aubameyang netted what could be an important away goal with 23 minutes remaining.
Gianluca Mancini’s early goal was all that separated AC Milan and Roma in their all-Serie A tie at the San Siro.
Milan controlled most of the game but did not recover from Mancini’s effort with Olivier Giroud directing a short-range target on to the crossbar in the closing moments.
Aston Villa clawed a slender advantage from their Europa Conference League quarter-final against Lille after emerging with a 2-1 first-leg win at Villa Park.
Goals in either half from Ollie Watkins and John McGinn saw Villa lead their first European last-eight tie since 1998 and give boss Unai Emery victory in his 1,000th match as a manager.
Bafode Diakite’s late header gave the French side a lifeline just as it looked like they would head home frustrated by Villa goalkeeper Emiliano Martinez, who had made a string of big saves.
Simeone insists Atletico 'cannot stop pushing' after narrow Mallorca win
Diego Simeone insists Atletico Madrid "cannot stop pushing" in their pursuit of Champions League qualification after a narrow 1-0 victory over Mallorca.
Los Rojiblancos tightened their grip on fourth place in LaLiga, with Rodrigo Riquelme's fine individual effort in the fifth minute enough to secure back-to-back wins.
With four games remaining, Simeone's side moved onto 67 points, six clear of fifth-placed Athletic Bilbao, who they beat 3-1 last weekend.
The Atleti boss was thrilled by his players' performance levels, but has urged them not to rest on their laurels.
"The team interpreted the plan very well," he said. "The commitment was incredible from [Angel] Correa to [Jan] Oblak to play an intelligent game from a defensive point of view.
"After the goal, we controlled the game. We defended as a team and did a great job. We need to continue improving, and we can't stop pushing until the season is over."
Echoing his manager's thoughts, defender Axel Witsel told Movistar Plus+: "It was very important to win. We wanted to win and stay six points ahead. We have to keep it up.
"After Riquelme scored a fantastic goal, we managed to stay well-organised to secure the result."
'It hurts to lose' - Inzaghi apologises after Sassuolo defeat
Simone Inzaghi admits "it hurts to lose" following Inter's surprise 1-0 defeat by relegation-threatened Sassuolo.
The newly crowned Scudetto winners suffered only their second loss of the season in Serie A, as Armand Lauriente's first-half goal was enough to give the 19th-place hosts victory at Mapei Stadium.
Sassuolo, who boosted their survival hopes, subsequently completed the league double over the Nerazzurri, having also prevailed 2-1 at San Siro in September.
Meanwhile, Inter were beaten by a team in the bottom two for the first time since November 2014, with Inzaghi urging his players not to be distracted by their title triumph.
"We started sluggish and didn’t have the right approach to the game," he told Sky Sports Italia. "I'm sorry for the defeat, but credit must be given to Sassuolo for a performance of great effort and sacrifice.
"It's right to enjoy [our Scudetto victory], but there are still three games to go and we have to focus. It hurts to lose, and it should hurt."
After guiding Inter to their 20th Serie A crown, Inzaghi is hopeful he can keep the majority of his squad intact ahead of next season.
However, the Nerazzurri boss did emphasise the club's need to strengthen before launching their Scudetto defence.
"I already told the club that I want to go into next season with all the players I had this term, not losing a single one," he said. "Considering all the games we need to play and the length of the season, we do need a bigger squad."
Inter Miami 6-2 New York Red Bulls: Messi makes more MLS history as Suarez scores hat-trick
Lionel Messi had a hand in all six goals while Luis Suarez scored a hat-trick as Inter Miami overcame the New York Red Bulls 6-2 at Chase Stadium.
The Eastern Conference leaders were on a three-match winning streak in MLS, but fell behind to Dante Vanzeir's opener in the 30th minute.
However, the hosts turned the match on its head after the break, with Messi assisting a brace for half-time substitute Matias Rojas either side of getting on the scoresheet himself.
Suarez then took centre stage with a hat-trick inside 13 minutes - all assisted by his former Barcelona team-mate - while Emil Forsberg's stoppage-time penalty was a mere consolation for the visitors, who are now without a win in four.
Data debrief
Messi broke two more MLS records following yet another inspirational display for the Herons.
The eight-time Ballon d'Or winner's six goal contributions and five assists were both the most recorded by a player in a single game.
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