Promoted Granada moved into first place in La Liga after a convincing 2-0 win over Barcelona on Saturday took them to 10 points and into a tie with Sevilla in top spot.
The result marks the worst start to a La Liga season in 25 years for the Catalan giants.
The hosts, who had only beaten Barca once in their last 20 meetings, took an early lead when Ramon Azeez headed home from close range to make it 1-0 in just the second minute.
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Lionel Messi, still working his way back to full fitness and playing in his first La Liga game of the season so far, was brought on at half-time for Carles Perez to help Barca find their way back into the game.
However, it was Granada that would score again when a handball in the penalty area was called on Arturo Vidal and Alvaro Vadillo converted from the spot after a consultation with VAR confirmed the ruling.
"This defeat hurts us and makes us very worried and we need to really take a hard look at ourselves if we are to improve," Barca's Luis Suarez said after a second defeat in five league games confirmed the club's worst start since the 1994-95 season.
"It was very hard for us after going behind in the first few minutes, we didn't manage to dominate the game in any way. We need to analyse what has gone wrong in these away games; we are obviously concerned about the lack of chances we are creating."
Barca also have the joint-worst defensive record in the league along with Real Betis, having conceded nine times in five matches.
"It's clearly not a very good statistic for us and not in line with what we have been doing in the last few years," said Barca coach Ernesto Valverde.
"I'm worried because away from home we're not getting good results. No wins from four away games this season is a clear symptom that we are not in a very good situation."
The Catalans, who have failed to win any of their last seven away games in all competitions, are seventh in the La Liga standings with seven points after five matches, while Granada sit on the summit with 10 points.
Second-placed Sevilla also have 10 points and can go clear at the top when they face Real Madrid on Sunday, while Atletico Madrid are third on 10 points after drawing 0-0 with Celta Vigo
Barca have enjoyed mixed fortunes at Granada's Nuevo Los Carmenes stadium in recent years and travelled there after an uninspiring 0-0 draw in Dortmund in their Champions League group, having lost away to Athletic Bilbao and drawn at promoted Osasuna.
The Catalans clinched the title in Granada on the final day of the 2016 season but lost 1-0 there in 2014, a defeat which played a huge role in Atletico Madrid winning the league at their expense.
Granada spent the last two seasons outside Spain's top flight and despite tickets being priced at €110 the stadium was full to capacity and rocking from kick-off to the final whistle, the atmosphere boosted by Azeez's early goal.
As Granada celebrated an unlikely victory and their even more unlikely status as league leaders, Barca were left to contemplate the fact that they have failed to win any of their last seven competitive games away from the Camp Nou.