The world record holder had qualified fastest for the final by more than four seconds as she looked to add to her 400m freestyle silver from earlier in the Games.
Russia’s Olesya Vladykina led the race out but Frederiksen began to assert her dominance at the half-way stage, turning first in a 50m back world record of 37.05 secs.
And the Briton powered clear down the back 50m, winning by a body length as she touched in 1:17.00 ahead of USA’s Jessica Long and Vladykina.
“That race was absolutely everything to me,” said the Frederiksen. “Yesterday I was really nervous coming in to it, I was nervous this morning and I was nervous again tonight.
“But I was determined that I was going to fight to win it and that’s what I did.
“I knew I had to go out strong and I had a funny feeling the girls were catching me down the last 25m and last 15m because the crowd were getting louder and louder.
“So I just had to keep pushing and get to that wall.”
Stephanie Millward won her third medal of the Games with a European record in the 400m freestyle.
The world silver medallist had qualified second fastest for the final and saw off the challenge of Australia’s Ellie Cole to take silver behind South Africa’s defending champion Natalie du Toit, who destroyed the field.
Millward eventually knocked more than two seconds off her old European marker with a time of 4:40.01 to add to her 100m backstroke silver and 4x100m freestyle relay bronze from earlier in the Games.
“I tried to use Natalie as my pacer and in the end, that was an absolutely fantastic result,” said Millward.
“I knew I had a really good back end and on that last 50m I was trying not to get too excited but I thought, she’s not going to catch me on this.”
Matthew Walker won his 12th Paralympic medal, his first of London 2012, with bronze in the 50m freestyle.
It was a poignant moment for Walker, who took a picture of his late father on to the podium with him as he finished behind American Lantz Lamback and China’s Pan Shiyun.
The 34-year-old has now won individual medals at four consecutive Paralympic Games and admitted he couldn't have given any more in pursuit of a fourth Paralympic gold.
"The young guns are fast and I'm getting on a bit now but I did my best and it's another medal to add to the 11 I've already got," said Walker.
"I wanted to get a gold but I gave it everything and couldn't have done any more.
"Everybody knows that it's been tough for me this season but it's splash and dash and I didn't have enough in me in those last five metres.
"I swam my heart out and that's all I could have done. It's a medal and at these Games the competition is really, really tough."
Ellie Simmonds added an unexpected 50m freestyle bronze to her burgeoning London 2012 medal tally.
The 17-year-old, who has also won 400m freestyle and 200m medley at the Games, admitted she hadn’t prioritised the short sprint despite being world champion in the event.
But having qualified fourth fastest, Simmonds put herself in the mix and snatched her third medal of the Games at the death, beating Germany’s Tanja Groepper by just 0.17 as she finished in a season’s best 36.11.
“That’s a massive surprise really because this is my fourth best event and I was going in fourth,” said Simmonds.
“I was hoping to go for a personal best but I think a bronze medal overtakes that at my home Paralympic Games.
“I’m just so happy to be on the podium again and it sets me up really nicely for my 100m freestyle.”
Oliver Hynd scooped his second Paralympic medal of his debut Games with bronze in the 100m backstroke.
The 17-year-old, who won 400m freestyle silver on the second day, held off teammates Thomas Young and Sean Fraser in the closing metres to clock a season’s best 1:08.35.
Russians Konstantin Lisenkov and Denis Tarasov had qualified in first and second and claimed the top two spots on the podium.
But the battle between the British trio had the home crowd in raptures as world bronze medallist Young ultimately came fourth in 1:08.91 and Beijing bronze medallist Fraser fifth in 1:09.67.
“I’m actually not that happy with the time,” said Hynd. “I wanted to go a bit faster than that but I’m still on the podium so I’m obviously delighted with another medal.
“I’ve got another big race tomorrow so I’ll go back and rest as much as I can now for that.”