Tottenham have not won any of their past 36 Premier League games after falling behind, so the outcome already looked ominous by half-time.
They controlled the first 20 minutes, with Villa goalkeeper Zion Suzuki stopping attempts from Savio and Archie Gray. However, their failure to score left them exposed to a response at the other end.
Villa’s breakthrough therefore felt increasingly likely as first-half stoppage time arrived.
Andy Robertson attempted to prevent a corner but instead presented possession to John McGinn. After Boubacar Kamara’s effort, Manzambi turned the ball in from close range. Tottenham’s problems were compounded by an injury to Van de Ven, who had to leave the field following a blow to the face.
A number of Tottenham supporters missed the opener while leaving their seats for the interval, and several thousand more departed before the final whistle.
Many headed for the exits after Buendia fired a superb 25-yard strike into the top corner in the 79th minute, meaning they did not see the late attempts from Gallagher and Van Hecke.
De Zerbi said: “My main concern is how we allowed the opening goal while playing with 10 men. We needed to show greater strength, communicate better and remain compact defensively.
“For that period, I moved [Rodrigo] Bentancur into central defence and used Mateus Fernandes in midfield. A team must be capable of competing with 10 players, even if it has to do so for 70 minutes.
“After the break, [Mohammed] Kudus had a goal ruled out for offside. I am unsure whether some players became tired, but the goal we then conceded was unacceptable. We knew Aston Villa had increased their use of long passes by 86% compared with last season.
“We discussed that repeatedly before the match, yet we now have to account for another result like Newcastle, where we performed well in the first half and still ended up losing. I accept responsibility.
“The responsibility is mine, but at that stage we must defend properly and stay organised. The senior figures in the team also have to step forward and lead.
“I am deeply disappointed and frustrated by the display. We cannot allow a match to slip away in that manner, and the second goal we gave up was astonishing.”
Villa supporters aimed chants of “Sacked in the morning” at De Zerbi, who appeared to have few answers after his team went two goals down.
It represented Tottenham’s poorest opening to a top-flight campaign since 2008-09, when they likewise collected only two points from their first five fixtures.
Juande Ramos lost his job after three further defeats before Harry Redknapp guided the club to an eighth-place finish. Spurs have also begun a season with five consecutive league matches without victory for the first time since 1986.
Former Brighton forward Glenn Murray nevertheless believes De Zerbi should be given more time.
“He is attempting to create something new, and that process requires patience,” Murray said. “If emotion is set aside and the statistics are considered, they have registered more shots in three of their previous four matches, enjoyed more possession and recorded more touches inside the opposing penalty area.
“Those are encouraging signs, so patience is important. The underlying numbers suggest he can improve the results. Roberto De Zerbi and the many new arrivals need time to develop an understanding and become a cohesive team.”
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