Kevin Kampl's second-half strike leaves Spurs frustrated after being completely outplayed in apoor performance, by their standards, under the lights of Wembley.
Tottenham looked far from the side they were that qualified for thecompetitionafter thesecond half brought the game alive in which Leverkusen capitalised on a shot partially blocked twice to seal a 1-0 victory following two previous penalty shouts from Spurs.
Spurs invited early pressure on themselves, looking far different from the organised unit we're soused to seeing in the league with possession frequently changing hands in the initial stages.
MauricioPochettino wasforced into an earlysubstitution with Vincent Janssen coming on for Moussa Demeble only30 minutes in, which saw Son drop from his makeshift role up-top.
#THFC sub: @mousadembele is replaced by @vincentjanssen. #COYS
Kyle Walker gifted the best chance of the half to Leverkusen with a poor clearance playing in Brandt only for Vertonghen to make two crucial blocks first that of Brandt's shot and then the rebound hit from Hernandez.
Just short of the stroke of half-time Alli saw his goal disallowed after being played by Janssen who hadfouled his man in the set-up.
Tottenham kicked off their second-half in far better fashion than the first with Alli appealing for a foul just inside the box, which the refereewaved awayas Eriksen's follow-up shot from distance looked like it wascreeping in, but fell just wideof the post.
The London side then had a minorcall for a penaltyafter some shirt tugging between Tah and Janssen. Before a surging run from Walker saw everything fall right apart fromthepivotalshot.
Eric Dier then caused some trouble for his side only for Hugo Llrois to save Spurs again, much like in the reverse fixture in Germany.
However,theFrenchshotstoppercouldn'tstopKampl'seffortafterapartiallyblockedshot
fromAranguiz fell right to theSlovenian'sfeet totake his side 1-0 up at Wembley.
Eric Dier, who had been below par for the majority of the game, looked to have brought his side back in the game after hestruck a great free-kick only to strike the bar, similar to the goalhe scored for England over the summer.
Dutch striker Janssen then looked set to capitalise on the rebound, but failed to do score as Bayer 04's defence scrambled the ball away to maintain their lead.
Tottenham Lineup: Lloris, Walker, Dier, Vertonghen, Davies, Wanyama, Dembele (Janssen 30'), Sissoko, Alli, Eriksen (Winks 66'), Son (Nkoudou)
Bayer Leverkusen Lineup: Leno, Henrichs, Toprak, Tah, Borges, Kampl, (Volland 85')Baumgartlinger, Aranguiz (Havertz 86'), Brandt, (Calhonoglu 70'),Mehmedi, Hernandez