The 16-year-old missed out on bronze in the 100m backstroke on Friday by just 0.08 to the Dutchwoman, but there was no denying her as she stormed past the world champion on the final 50m to win in 2:12.63.
A two-second personal best was also enough for a Paralympic record for Applegate in her final appearance of the Games.
“I had to give everything I have because that was my last race and I knew it wouldn’t matter if I collapsed at the end of the race,” said Applegate whose teammate Natalie Massey finished sixth.
“I’m normally a sprinter so that definitely helped me at the end of the race. My PB was 2:14 so to knock two seconds off it was amazing. Everyone has given me so much support which has really helped.”
James Clegg won the first Paralympic medal of his career with bronze in the 100m butterfly just an hour before his sister Libby took silver in the 100m at the Olympic Stadium.
After setting a British record 59.99 to qualify third in the heats, the 18-year-old – making his international debut in London – turned in fifth before storming back to finish in a minute dead.
He out-touched USA’s Tucker Dupree by just 0.15 for his medal in a race won by Russia’s Roman Makarov.
Clegg said: “I’m really happy to be able to stand on the podium. It hasn't really sunk in yet. I guess that will come later.
“The swim was good. I knew there was a guy ahead of me and I really wanted to catch him and I did.
“I was planning to put my headphones on and ignore the noise but Libby told me to listen to it and use it to spur you on and it really did.”
Minutes after Clegg’s medal, teenage sensation Hannah Russell claimed her second medal of her debut Paralympics as she also won 100m butterfly bronze.
The 16-year-old, who won 400m freestyle silver on the opening night in London, sliced 1.46 seconds off her British record to touch home in 1:08.57.
“I’m absolutely over the moon,” said Russell. “To come here and get another medal in one of my main events is fantastic.
“Coming back from the 400m free with a big PB gave me a lot more confidence and hopefully I can get some more this week.”