Visitors Leeds took the lead through Stuart Dallas shortly before half-time, just minutes before captain Liam Cooper was sent off for a challenge on Man City striker Gabriel Jesus.
In the second half, City pressed for an equaliser that eventually came via Ferran Torres in the 76th minute, and the top-flight leaders looked the likelier of the two teams to grab a winner.
But Dallas struck again for Marcelo Bielsa’s side in the dying moments to secure all three points for Leeds.
“In the best moment that we have, we concede a goal,” City coach Guardiola told Sky Sports at full-time.
“We were not aggressive enough in those areas. We arrive in the final positions and today we could not score [enough goals].
“After the sending-off for them, we didn’t create as much chances. But when we play against teams set up in that way, with the pace they have on the counter-attack, we have to avoid the counter-attack – before the goal, we concede another one.
“They have a team where the transitions are fantastic and, yeah, I congratulate Leeds.
“It was not much clear, the chances; we had shots, but not [many clear chances]. We arrive in the final third, but after that we could not create much.”
When asked whether he viewed the defeat as a “freak result”, Spaniard Guardiola said: “When I play a game, always I am thinking we can win, we can lose… We prepared for the game as good as possible. The guys… we tried, but we couldn’t do it.”
Earlier this week, City were 2-1 victors at home to Borussia Dortmund in the first leg of the teams’ Champions League quarter-final.
The second leg takes place next week, with City then taking on Chelsea in the FA Cup semi-finals.
City are still 14 points clear of second-placed rivals Man United in the Premier League, though Ole Gunnar Solskjaer’s team have two games in hand over the leaders.