Tuesday of Gameday 2 was a very bad night for Mauricio Pochettino's Spurs who lost by a record 7-2 to Bayern Munich at the Tottenham Stadium.
Serge Gnabry scored four second-half goals for Niko Kovac's German champions.
Meanwhile, there were also wins for PSG, Atletico Madrid, Juventus, and Manchester City but not Real Madrid who were held 2-2 at home by Club Brugge.
On the Wednesday night holders Liverpool conceded three goals at Anfield but still managed a best of seven victory over newcomers Red Bull Salzburg.
Barcelona, Dortmund, Lyon, Ajax, Zenit St Petersburg, and Chelsea were the other winners in Round 2 of the group stage.
A late James Milner penalty gave Liverpool victory against Leicester and they retained their 100% league record.
And the men from Anfield will go into the international break eight points clear after Manchester City's surprise 2-0 home defeat by Wolves.
Frank Lampard's Chelsea are now 5th following their impressive victory at Southampton.
But record title-holders Manchester United lost to Newcastle and are now a distant 12th in the EPL.
Real Madrid stays top after beating second-placed Granada 4-2 at the Bernabeu.
Their great rivals Barcelona remain close behind - the Catalans beat Sevilla 4-0 at Camp Nou with Lionel Messi among the scorers.
Inter conceded their 100% league record after Gonzalo Higuain got the winner for the champions, and new leaders, Juventus at San Siro.
PSG asserted their control in Ligue 1 by defeating Angers 4-0 at the Parc while Nantes are two points behind in second after beating Nice.
There is a (long) name from the past, Borussia Moenchengladbach, leading the rest in Germany.
That was after they beat Augsburg 5-1 at Borussia-Park and old rivals Bayern Munich slipped up at home to Hoffenheim.
And Wolfsburg moved into second position following a single goal win over promoted Union Berlin.
Can unlikely leaders Famalicao continue their minor miracle by winning against Porto when the league returns?
AFRICAN PLAYER NEWS & GOSSIP
Possibly moving to AC Milan - Mohamed Elneny (Egypt)
Chad, Sao Tome e Principe, South Sudan and the Gambia have progressed to the group stage qualification for the Africa Cup of Nations 2021.
Ukraine became the latest country to qualify for the finals of Euro 2020 after they beat Portugal 2-1.
And there were also wins for Serbia, Iceland, Albania, Kosovo, and England (6-0 against Bulgaria in a game marred by racist incidents)