Manchester City's Spanish manager Pep Guardiola. AFP
With just 12 minutes left at the Amex Stadium, Guardiola's troubled side were clinging onto the lead given to them by Erling Haaland in the first half.
But the Premier League champions collapsed in the closing stages as Joao Pedro equalised before Matt O'Riley bagged Brighton's winner seven minutes from full-time.
For the first time in his glittering career as a manager with City, Bayern Munich and Barcelona, Guardiola has been beaten four times in a row.
It was also the first time City had lost four successive games since a run between April and August 2006 under Stuart Pearce.
"Today we played really good in the first half but we couldn't finish the game," Guardiola said.
"We were not consistent to maintain our game and our intensity and press and be aggressive for 90 minutes.
"The level we are playing is really good in certain moments but we are not able to continue for a long time.
"I'm pretty sure when the players come back (after the international break) and we make some individual qualities in the team, we'll be back."
After exiting the League Cup to Tottenham and suffering a first league loss since December at Bournemouth, City were thrashed 4-1 by Sporting Lisbon in the Champions League in midweek.
The slump continued as they failed to kill off Brighton before the second half implosion that threatens to derail their bid for a fifth successive Premier League title.
Second-placed City are five points behind leaders Liverpool, who beat Aston Villa 2-0 at Anfield just hours after the champions' loss.
Injury issues have been key to City's malaise, with Manuel Akanji and Nathan Ake only fit enough for the bench, while Ruben Dias and John Stones were not in the squad, meaning 19-year-old Jahmai Simpson-Pusey was given a first league start in central defence.
'Get back to winning'
The makeshift backline cracked under pressure in the second half, leaving Guardiola to deal with the worst period of a glittering managerial career featuring six titles in eight years with City, as well as countless trophies during his spells at Barcelona and Bayern Munich.
"It can always happen one time in a lifetime, right?" said Guardiola of his fourth consecutive defeat.
"Always there's a first time. We've lost two games in the Premier League and we have to change it, get back to winning. We're in the position that we are in the table.
"When the players come back I don't have any doubt that we will be back to our best.
"Normally people lose games, right? Always there's a first time in life. This is my challenge, our challenge, and I like to face it.
"I will not step back at all. More than ever I want to do it. We will try again."
Guardiola had insisted he would solve City's problems but he has so far been unable to come up with the answer to their mounting crisis.
Hinting City might not be able to make it to five successive titles, Guardiola added: "Four defeats in a row. We have to change things quick.
"Maybe after seven years winning six Premier Leagues, maybe one year another team deserves it."
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