Winnifrith had qualified second-fastest for the final behind Neutral Paralympic Athlete and defending champion Mariia Pavlova.
But Pavlova started the final strongly and maintained her dominance, beating her own world record by 0.77 seconds with a time of 1:26.09 as the Briton set a new personal best of 1:29.69 ahead of Canada’s Tess Routliffe (1:31.38).
“I’m really happy with that swim. Much as I wanted the gold, it’s still a silver medal and a lifetime best,” said the Kent swimmer, who, like her idol Ellie Simmonds, has now won a Paralympic medal aged 13.
“I knew I had to fight for a medal. I tried to catch the other girl as much as possible but today it wasn’t enough.
“Ellie has influenced me so much and I’ve now met her a few times and she has really helped me.”
Winnifrith is Britain’s youngest Paralympic swimming medallist since Scotland’s Abby Kane claimed S13 backstroke silver at Rio 2016, six weeks after her 13th birthday.
Joanne Round, later Joanne Rout, remains Britain’s youngest Paralympic champion after she won two relay golds at the 1988 Seoul Games aged 12.