Visiting Atalanta shocked top favourites Liverpool 3-0 at Anfield in the Europa League quarter-finals on Thursday in another major setback for Jürgen Klopp's men, while unbeaten Bayer Leverkusen marched on with a 2-0 win over West Ham United.
Gianluca Scamacca scored a 38th and 61st-minute brace, and Mario Pasalic wrapped up matter in the 83rd to put the Italians into pole position for a semi-final berth in their home leg next week.
Defeat for Liverpool came after they were held 2-2 by Manchester United on Sunday and lost the Premier League lead to Arsenal in a three-way title fight also involving title holders Manchester United.
Bundesliga champions-elect Bayer Leverkusen defeated Conference League winners West Ham from late goals by Jonas Hofmann and Victor Boniface who had both come on in the 76th.
Xabi Alonso's Leverkusen stretched their unbeaten run all season to 42 matches, of which they have won 37, and keep their treble chances alive. They can clinch a first Bundesliga title on Sunday and are also in the German Cup final.
In the other games, last year's finalists Roma drew first blood in an Italian duel with a 1-0 victory at AC Milan, and Benfica defeated Olympique Marseille 2-1.