The 17-year-old, who has dwarfism, finished the race in the Aquatics Centre in a time of 36.11s.
"That is a massive surprise," said Simmonds. "This is my fourth event and I was going into the final fourth so I didn't expect that.
"I was hoping to go for a personal best and see what happened and so to get a bronze, I will definitely take that. To be on the medal podium again ahead of the 100m later this week is a great sign."
The British Paralympian clinched gold in the S6 400m freestyle as well as the SM6 200m medley.