The score was locked at 2-2 when the German midfielder was put on the pitch to replace Alex Iwobi in the 70th minute.
In the 84th minute, Ozil gave away possession just moments before Charlie Austin scored to make it 3-2.
Instead of making a simple pass, the 30-year-old tried to pull off a dummy when he received the ball in Southampton's half.
Ralph Hasenhuttl's men charged up the pitch and Shane Long's delivery picked out Austin in the box for a simple finish.
The Gunners lost the match 3-2 and their 22-game unbeaten run in all competitions came to a disappointing end at St Mary's.
And the furious fans turned to Twitter to pile the blame on Ozil.
One said: "Ozil… I understand a dummy outside the box, I don't understand a dummy attempt in the middle of the pitch."
Another added: "Massive fan of Ozil but days like today illustrates why people target him so much.
"That awful dummy in the build up to Southampton's third goal. Came on to inspire us and ended up helping to cost us."
Mesut Ozil's Premier League stats from this season
- Appearances – 11
- Goals – 3
- Wins – 5
- Losses – 3
- Goal per match average – 0.27
- Headed goals – 0
- Goals with right foot – 0
- Goals with left foot – 3
- Shooting accuracy – 60%
- Yellow cards – 1
- Red card – 0
- Fouls – 5
- Offsides – 4
- Average passes per match – 44.45
- Cross accuracy – 73%
- Tackles – 8
- Tackle success rate – 25%
While another stated: "That was Ozil's fault for trying some stupid dummy."
Ozil returned to action for Arsenal on Thursday during the 1-0 win over Qarabag after he missed five games with a back injury.
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