Spurs manager Jose Mourinho made two changes to the team that started in the 3-2 win at Aston Villa on Sunday as midfielders Gedson Fernandes and Giovani lo Celso came in for Eric Dier and the injured Son Heung-min.
Ethan Ampadu, on loan from Chelsea, secured a place in RB Leipzig boss Julian Nagelsmann’s starting XI as defender Dayot Upamecano was suspended and Ibrahima Konate and Willi Orban were both out due to injury.
Leipzig seemed keen to make a good impression in their first-ever meeting against Spurs as the German Bundesliga outfit almost scored twice inside the opening two minutes.
Patrik Schick had an effort flash just wide from the edge of the area, before Angelino saw his strike from a tight angle hit Hugo Lloris and deflected wide off the post.
Steven Bergwijn had Spurs’ first effort of note on seven minutes when he was teed up by Lo Celso from a cleared corner.
Leipzig continued to dominate possession and they again went close on 27 minutes when Angelino’s low cross was just too far ahead of Timo Werner’s outstretched boot, although the offside flag was up against him.
Lloris kept Spurs level with a superb save on 36 minutes as he parried Werner’s fierce angled strike to safety when it seemed certain that the prolific forward would score.
Having been fortunate to go in at the interval on level terms, it was Spurs who had the first chance after the break when Serge Aurier found Lucas Moura in the area and his effort forced a smart save from Peter Gulacsi.
However, Leipzig got their noses in front from the penalty spot on 58 minutes when Werner blasted his effort past Lloris after Ben Davies bundled over Konrad Laimer inside the Spurs area.
It was almost 2-0 on 62 minutes when Werner allowed an Angelino pass to run on to Schick whose strike was parried away to safety by Lloris.
Spurs were inches away from equalising on 73 minutes when Lo Celso’s curling left-foot effort appeared to be heading for the net until Gulacsi managed to divert it on to the post with a finger-tip save.
The hosts pushed for an equaliser in the late stages but they couldn’t find a way through as Lucas missed the best chance when heading over from six yards out on 89 minutes.
Therefore, Leipzig will take a lead and a potentially crucial away goal into the second leg in Germany in three weeks’ time.