It is advantage Spurs courtesy of Heung-Min Son's goal and Hugo Lloris's penalty save.
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Heung-Min Son struck the only goal as Tottenham earned a narrow lead to take into next week's quarter-final second leg at Manchester City.
Son showed great composure with 12 minutes left, keeping the ball in the field of play and then stepping inside Fabian Delph before firing under Ederson. But Spurs were equally indebted to Hugo Lloris, who denied Sergio Agüero from the spot early on.
The only dampener for Mauricio Pochettino was the sight of Harry Kane being helped off the pitch midway through the second period. Up stepped Son, though, to secure a memorable win for Spurs in their first UEFA Champions League outing at their new stadium.
View from the stadium: Daniel Thacker
This was a slow-burner, the football at times matching the excellent atmosphere generated by the Tottenham faithful on the first European night at their new home; at other times developing into a midfield war of attrition. Lloris's 13th-minute penalty save gave Spurs a platform to grow into the game, before Son scored late to hand Tottenham a precious advantage ahead of the journey north.
Man of the match: Heung-Min Son
Son took up the scoring baton when Kane was injured earlier this year and with the Tottenham skipper off the pitch with another knock he did it again, his goal testimony to his tirelessness in the Spurs cause. And he did it, typically, by chasing a lost cause. After hitting the first senior goal at this arena, here was another collectors' item – the first in Europe, and one that gives his side real hope.
2: This was only Tottenham's second victory in their last 17 matches against City (L11 D4).
5: City have lost all five of their European games against English opponents.
100%: Hugo Lloris has saved three penalties out of three in 2019.
33%: Qualifying included, Agüero has converted just three out of nine penalties in the UEFA Champions League.
2: Son claimed the first Premier League and the first UEFA Champions League goal at the new Tottenham Hotspur Stadium.
3: Spurs are the only team to have won all of their games in this season's UEFA Champions League knockout rounds.
4: Tottenham have kept four clean sheets in their last five UEFA Champions League matches.
13: Thirteen of Tottenham's 14 UEFA Champions League goals this term have come after half-time.
What does it mean?
Having successfully fended off the blue half of Manchester here, Tottenham will head into the lion's den next Wednesday with their noses in front. Pep Guardiola's men have won 12 out of 12 at home in 2019 but a Spurs goal could nonetheless knock them off their stride; Lyon have already demonstrated this season that City aren't impervious on home soil. But they are mighty good.
Already-relegated Huddersfield are the latest visitors to Spurs' new stadium on Saturday, before Pochettino's charges play successive games away to City – in the second leg on 17 April and in the league just three days later.
City's relentless run-in continues apace with a trip to Crystal Palace on Sunday prior to those back-to-back matches against Spurs and what is shaping up as a title-deciding visit to city rivals Manchester United on 24 April.