Thierry Henry remains without a win since taking charge of Monaco after they were beaten 4-0 at home by Club Brugge in Group A.
Hans Vanaken scored twice in the space of five first-half minutes to put the visitors firmly in control and Wesley made it three with a superb curling shot to put the game beyond the Ligue 1 strugglers before half-time.
Brugge skipper Ruud Vormer capped a fine display with a well-taken fourth late on.
Also in Group A, Atletico Madrid gained revenge for their 4-0 defeat to Borussia Dortmund a fortnight ago with a 2-0 victory at Wanda Metropolitano.
Group D leaders Porto were comfortable 4-1 winners at home to Lokomotiv Moscow, with Hector Herrara giving Porto the lead after two minutes.
Moussa Marega made it two with a powerful run and finish but Lokomotiv Moscow pulled one back through substitute Jefferson Farfan’s neat header.
Jesus Corona made the game safe for Porto and Monteiro Otavio added a fourth in stoppage time.
Schalke pulled clear in second place with a 2-0 win at home to Galatasaray.
Guido Burgstaller took advantage of a goalkeeping error from Fernando Muslera to curl in the opener after four minutes and Mark Uth made it 2-0 with a cool finish.
