Back after 13 months on the sidelines with a hip injury, Lamela came off the bench on 77 minutes and 80 seconds later, played in Harry Kane to rifle home for 2-1.
That proved the highlight of the night though as we laid siege to the home goal in the second half without finding an equaliser.
Our best chances fell to Christian Eriksen and Fernando Llorente but somehow that second goal proved elusive.
In the end, we paid for conceding two goals in the first half, taken well by Jamie Vardy and Riyad Mahrez.
Mauricio Pochettino made four changes to the team that started against West Brom on Saturday. Serge Aurier, Danny Rose, Mousa Dembele and Moussa Sissoko came in for Kieran Trippier, Ben Davies, Harry Winks and Heung-Min Son. Lamela's involvement as a substitute was his first since our EFL Cup tie at Liverpool on October 25, 2016.
GOAL: LEICESTER 1-0 SPURS - JAMIE VARDY - 13mins
It was an open start, Rose cleared Wes Morgan's header off the line and Leicester struck first on 13 minutes. Marc Albrighton picked up the ball on the left touchline and floated a pass in to Vardy. There didn't look too much on but the England striker fashioned a first-time, looping volley over Hugo Lloris into the far corner.
CHANCES: CLOSE TO AN EQUALISER - 15-32mins
Despite the goal, we looked capable of creating chances. The best out of a number of promising positions fell to Sissoko, who was clean through on Kasper Schmeichel from Kane's pass but hit the goalkeeper's legs one-on-one. Kane fired over from the left angle on 23 minutes and Schmeichel was there again to make the block from Dele Alli after a quick break from a Leicester corner, this time Vicente Iborra was back to complete the clearance.
Above: Serge Aurier competes with Jamie Vardy.
GOAL: LEICESTER 2-0 SPURS - RIYAD MAHREZ - 45+1mins
A tough one to take on the stroke of half-time. We'd pushed for an equaliser but were caught on the break, Wilfried Ndidi found Mahrez right side and - just as we saw here two years ago - the winger cut inside onto his left foot and pinged into the top corner from 20 yards.
CHANCE: ERIKSEN DRILLS WIDE - 75mins
We dominated territory and possession in the second half but the clear-cut chances didn't arrive until later on. Son and Llorente had entered the fray by now and Son set up a golden chance for Eriksen on 75 minutes. His cross was initially missed by Eriksen but the ball hit Llorente and fell back at Eriksen's feet - he missed the target on the follow up.
SUBSTITUTION: LAMELA RETURNS - 77mins
After 13 months on the sidelines, Lamela made his return for Eriksen on 77 minutes.
GOAL: LEICESTER 2-1 SPURS - HARRY KANE - 79mins
It took just over a minute for Lamela to have an impact, his slide rule pass in to Kane rifled home by the striker. It was now very much game on as we sought a route back.
CHANCE: LLORENTE FIRES OVER - 85mins
The one that got away as Aurier burst down the right and fizzed in a cross that Llorente turned over from six yards. We had a couple of half-chances after that and appeals for a penalty waved away after Ndidi's challenge on Rose in added time. Dele curled just wide in the final seconds, our last effort.
MAURICIO POCHETTINO SAID
"I'm very disappointed with the performance in the first half, it was so poor. You need to compete, you need to fight first of all, then play football. You cannot play football if you don't compete and fight in the Premier League. That's why we're so disappointed. It's true the game was open and we had chances to score, maybe to draw, maybe to win the game but in the end, the result was against us because of the first half. It's an example that in football, you need to respect yourself, compete and then play."
ERIK LAMELA SAID
"There were some very hard times but in life, you need to keep going, always looking forward. I fought every day to be good, to train, to help my team-mates. I did my best always and that’s why, today, I’m here again. Today is another step. I am back on the pitch and it felt amazing to play again in front of the people but unfortunately we didn’t win."
Leicester City (4-4-2): Schmeichel, Simpson, Morgan (c), Maguire, Chilwell, Iborra, Ndidi, Mahrez (Gray 77), Albrighton, Okazaki (Choudhury 83), Vardy (Slimani 87). Substitutes (not used): Hamer, King, Dragovic, Amartey.
Spurs (4-2-3-1): Lloris (c), Aurier, Sanchez, Vertonghen, Rose, Dier, Dembele (Llorente 69), Sissoko (Son 57), Eriksen (Lamela 77), Dele, Kane. Substitutes (not used): Vorm, Trippier, Foyth, Davies.
Goals: Leicester City - Vardy 13, Mahrez 45+1; Spurs - Kane 79.
Yellow cards: Spurs - Vertonghen 20.
Referee: Anthony Taylor.
We're back on the road in the Premier League on Saturday with the short trip to Watford. Kick-off is 3pm. The Hornets went down 4-2 to Manchester United on Tuesday night.