The 20-year-old had to settle for silver behind Ukraine’s Yelyzaveta Mereshko in the 400-metres freestyle S6, an event Simmonds had won at two Paralympics and two previous World Championships.
Simmonds was one of five British athletes to claim silver medals at Tollcross pool alongside her fellow West Midlands swimmer Tully Kearney, Scottish pair Andrew Mullen and Scot Quin, and City of Sheffield’s James Crisp.
There was a sixth British medal for Susie Rodgers, who collected a bronze.
Seven-times world champions Simmonds had recorded the fastest time in qualifying and went head to head with Mereshko until the final length of a two-horse race but finished eight-tenths of a second behind in five minutes, 22.54 seconds.
Simmonds said: “I’ve been the gold medalist since 2008 so it’s hard but I’m going to get ready for the 100 breaststroke and go out and enjoy it.”
Crisp began his sixth World Championships with a season’s best of 1:04.43 to finish the fastest qualifier in his favoured 100m backstroke S9.
That time would easily have been enough to claim gold in the evening but the 32-year-old recorded 1:05.12 to finish just behind Australia’s Brenden Hall.