Borussia Dortmund put in a fine display as they recorded a 6-0 demolition of Legia Warsaw in Poland.
Mario Gotze, Sokratis Papastathopoulos and Marc Bartra all scored in the opening 18 minutes and Raphael Guerreiro, Gonzalo Castro and Pierre-Emerick Aubameyang added more goals after half-time as Dortmund stormed to the top of Group F.
In the group's other game, holders Real Madrid were two minutes away from losing at home to Sporting Lisbon before staging a late comeback to win 2-1.
Juventus were held to a 0-0 draw by three-time Europa League winners Sevilla in Italy in Group H, but Lyon had no such issues at home, recording a comfortable 3-0 success over Dinamo Zagreb.
Bayer Leverkusen, who led 2-0 after 15 minutes, could only draw 2-2 at home with CSKA Moscow in Tottenham's group.
Meanwhile in Group E, It was a landmark night for Spurs as they broke an English club home attendance with 85,011 watching at Wembley, yet the majority were left disappointed as Monaco emerged with a 2-1 win.
In Group G, Porto and Copenhagen shared the spoils having drawn 1-1, with ex-Cardiff striker Andreas Cornelius scoring for the visitors.
Claudio Ranieri's Foxes, last season's unlikely Premier League title winners, had lost both of their opening away games domestically but had no such trouble on the continent.
Finally, Sergio Aguero put his domestic suspension to one side to grab a hat-trick as Manchester City defeated Borussia Monchengladbach 4-0 in their rearranged clash in Group C.
Having seen the contest postponed on Tuesday night due to heavy rain in the north-west, Aguero opened the scoring with a near-post finish before converting a penalty to make it 2-0 prior to half-time.
And, though he will sit out the next two domestic fixtures due to a ban triggered after his elbow on West Ham's Winston Reid, the Argentinian showed his value to City in this competition by completing his hat-trick. He was then substituted and his replacement Kelechi Iheanacho added a stoppage-time fourth.