Gabriel Jesus thought he had scored a late victor to secure all three points for the Champions, but replays showed the ball had struck Aymeric Laporte's arm prior to the Brazilian finding the net.
But Tottenham hit back inside three minutes as Erik Lamela beat slow-to-react City keeper Ederson from the edge of the area. I hope that we fix the problem for the next season.
The Belgium worldwide was named City's Player of the Year in 2017-18 but was restricted to just 11 starts in the Premier League last term due to knee and hamstring injuries.
The use of the Video Assistant Referee is set to be the biggest talking point of the season, after Manchester City's last-minute victor against Tottenham was ruled out by the software.
MANCHESTER, ENGLAND - APRIL 03: Josep Guardiola, Manager of Manchester City looks on prior to the Premier League match between Manchester City and Cardiff City at Etihad Stadium on April 03, 2019 in Manchester, United Kingdom.
Substitute Lucas Moura scored a second Tottenham equaliser from Lamela's corner just after half time before the late drama denied City a victor and ended their run of 15 consecutive Premier League wins.
An outstanding game of football, with two teams of technically gifted players competing at a relentless tempo, was decided by a ruling which would never have been given under the previous laws on handling.
As City's players celebrated, Guardiola hugged Aguero and appeared to make up with the striker, but was then left deflated as VAR ruled the goal out for handball.
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It is only Matchweek 2, but few Premier League days will match this. It was the right decision that decided the goal.
However, the goal was disallowed, as Aymeric Laporte was adjudged to have handled the ball before it made its way to Jesus.
MF Rodri, 7 - Careful and composed in front of the back four.
MF Ilkay Gundogan, 6 - Brought back in at the expense of David Silva.
MF Kevin De Bruyne, 8 - Two attractive crosses from the right created two goals in the first half.
However, if anything Guardiola's men look stronger last season with Kevin de Bruyne restored to full fitness, while Spanish worldwide Rodri was slotted seamlessly into midfield. On that occasion, Raheem Sterling had a goal disallowed for offside by VAR in the third minute of injury time, denying City a place in the semifinals.
"It's always more hard in a big game but we nearly totally dominated them".
Pep Guardiola will probably now feel he was tempting fate last weekend when he discussed the intervention of the video assistant referee during the 5-0 win at West Ham.