Jabeur followed her fellow second seed Casper Ruud out of the tournament on Thursday, going down 6-1 5-7 6-1 on Rod Laver Arena in a match that finished well after midnight.
The Tunisian, a finalist at Wimbledon and the US Open last year, had set big ambitions for herself before the event but struggled in her first-round match and came unstuck here against classy Czech Vondrousova.
The 23-year-old reached the Roland Garros final as a teenager in 2019, losing to Ashleigh Barty, and has struggled to build on that but remains a hugely-talented player and she thrived in the slow conditions.
Jabeur was unable to find her range – making 50 unforced errors – and she was shown crying in the tunnel after walking off court.
Vondrousova was sidelined for much of last season following wrist surgery, and she said: “It’s amazing. After the surgery, coming back into the big tournaments. You never know how you’re going to do. I felt good, but the draw was super, super tough.
“Then also the late matches and everything, it was kind of crazy. So I’m just very happy to get the win.”
Fourth seed Caroline Garcia also faced a former grand slam finalist in Leylah Fernandez, who was beaten by Emma Raducanu at the US Open in 2021.
It was a contest with very little to choose between the pair but Garcia proved the stronger in the big moments, winning 7-6 (5) 7-5.
Garcia recovered from 2-5 in the first-set tie-break, and she said: “It feels like it was almost a robbery that I won the first set. I was down always. I couldn’t make a point on her serve.
“Me, I was struggling. I was saving break points. It was very important for my confidence, for sure.”
Fifth seed Aryna Sabalenka had no such worries, breezing past Shelby Rogers 6-3 6-1 but there was another upset as brilliantly-named American Katie Volynets defeated ninth seed Veronika Kudermetova 6-4 2-6 6-2.