Spurs’ run to the final last season was full of great escapes and comeback wins and they will need another after Timo Werner’s second-half penalty gave the Bundesliga side a deserved win in their first ever knockout game in this competition.
It also sees 32-year-old Leipzig coach Julian Nagelsmann, who has been dubbed ‘Baby Mourinho’ and is a rising star of European football, gain the edge over the man he has been named after.
But Spurs boss Jose Mourinho will claim this was not a fair fight as he was without two of his best attacking players, with the loss Son Heung-min on the eve of the match adding to that of Harry Kane.
The defeat would have been much worse had Hugo Lloris not produced a number of vital saves to keep Leipzig at bay, while Spurs struggled for clear opportunities at the other end.
Giovani Lo Celso had the best of them as his free-kick was turned on to the post, but it was a frustrating night for Mourinho.
Spurs will look to last season’s semi-final, where they turned around a similar first-leg defeat to Ajax with a dramatic night in Amsterdam, and there is the sense that something similar will be required in Leipzig on March 10.
While Nagelsmann was enjoying his first taste of knockout football in this competition, this was nothing new for Mourinho.
But rarely will he have gone into such a big game without two such key men as Son and Kane and their absence really set the tone.
Although Spurs’ problems were in attack, their frailties at the other end were immediately apparent as Leipzig had three golden chances inside the opening two minutes.
The hosts were sliced open down the right and Nordi Mukiele’s cross teed up Werner, but his shot was blocked by Davinson Sanchez.
Then from the rebound Angelino’s shot was turned onto the post by the leg of Lloris, who then saved Werner’s effort from close range.
Spurs, with no recognised striker on the pitch, were hoping that the pace of Bergwijn and Lucas Moura would be their main weapon and it was the Dutchman who had their best moment of the first half.
The mercurial Lo Celso played him in with a deft touch and, after turning inside, Bergwijn’s low shot was palmed away by Peter Gulacsi.
But from then on, it was a succession of missed chances for the visitors as Leipzig found holes in the Spurs defence at will.
Patrick Schick put a header just wide from a corner, Angelino had another effort blocked and Lloris was called into action again to deny Werner with a parried save.
The inevitable eventually happened just before the hour mark.
Werner’s chipped ball was met by Konrad Laimer and the Dane was clattered into by Ben Davies, with referee Cuneyt Cakir rightly pointing to the spot.
Werner made no mistake as he drilled into the bottom corner for a crucial away goal.
It should have been even worse for Spurs as Leipzig got in on goal with a slick counter attack, but Lloris came to the rescue with a fine save off Schick.
Mourinho’s side had to up the ante and Lo Celso came close to levelling matters in the 72nd minute, but his 25-yard free-kick was tipped onto the post by Gulacsi.
Their big moment came in the 89th minute, but Moura could not deliver as he did in Amsterdam last May.
Davies had space on the left and picked the Brazilian out perfectly, but his header went over the crossbar and it left Spurs with another mountain to climb in this competition.