The 24-year-old from Fleurimont, Que., won the women's 200-metre individual medley in a visually impaired class in world-record time.
"I was not expecting a world record," Grand'Maison said. "I did not expect to go that fast. That's the best prize, to be surprised at myself."
It was Grand'Maison's third medal in London after taking silver in both the 100 and 50 freestyle.
It also ended a dry spell at the top of the podium for Canada as her gold was the country's first since Tuesday.
With two days of competition remaining in London, Canada had five gold, 14 silver and eight bronze medals for a total of 27.
The Canadian team's stated objective is a top-eight finish in the gold-medal count. With two days of competition remaining, Canada was tied for 21st.
Day 10 was a multi-medal day for Canada with a gold, three silver and a bronze.
Also in the pool, Amber Thomas of Drayton Valley, Alta., claimed silver in the S11 400-metre freestyle.
At the track, wheelchair sprinter Brent Lakatos of Dorval, Que., earned his third silver medal of the Games by finishing second in the 200 metres.
Ottawa's Jason Joseph Dunkerly and his guide Joshua Karanja were silver medallists in the men's 5,000 metres for visually impaired athletes.
Virginia McLachlan of Windsor, Ont., earned bronze in the women's 100 metres in the T35 classification, which is cerebral palsy.
Grand'Maison was Canada's most decorated athlete at the 2008 Paralympic in Beijing with three swimming gold and a bronze. She also set two world records there. A shoulder injury last year threatened to end her career.
So she was relieved to gain another gold in what she saw as her last chance to get one. Grand'Maison races the 100-metre breaststroke Saturday, but feels she's a long shot for a medal there.
Grand'Maison eclipsed the previous world record in the 200 I.M. with a time of two minutes 27.64 seconds.
"The pressure is finally off," Grand'Maison said. "I have had a rough week. I have had highs and lows, but I have overcome all this.
"Tonight I am going to hug my coach, tell him I love him, see my family, tell them I love them. I'm going to cry on the podium."
Thomas, 18, won her first Paralympic medal after finishing fourth, fifth and sixth in previous swims in London.
In the 400 freestyle for visually impaired swimmers, the Canadian posted a time of 5:15.48 to finish second behind winner Daniela Schulte of Germany in 5:14.56.
"When I got to the end I was absolutely drained so I don't know if I could have pushed it any harder," Thomas said. "I never felt as nervous for a race as the one tonight."
Wheelchair racer Lakatos added silver to his growing collection of that colour by finishing second in the men's 200 metres. The 32-year-old was also a silver medallist in the 400 and 800 metres.
China's Li Huzhao won the 200 in 25.61 seconds. Lakatos posted the fastest time of his life in 25.85 as runner-up.
"There's nothing to be unhappy about as it's a huge PB for me," Lakatos said. "Obviously I didn't win but I gave it everything I had and the Chinese guy is just a little bit faster than me."
"It's been a great Games, I've got three medals and my first three medals, so I couldn't be happier."
Dunkerly and guide Karanja led the 5,000 metres until they were caught with just over two laps to go by Chile's Cristian Valenzuela and his guide Cristopher Guajardo. The Chileans won in 15:26.26 followed by the Canadians in 15:34.07
"They hung behind us a little pit, then passed us and we tried to go with them," Dunkerly said. "Josh was telling me exactly what was going on and they were just a bit stronger than we were. We were trying to close the gap, but they had a little more than we did today.
"Of course when you're leading for that long, it's tough when it kind of gets taken away from you, but we had our plan and committed to it and let the chips fall where they do."
Dunkerly, 35, won a pair of silver medals and a bronze at previous Paralympics in the 1,500. He and Karanja, a college steeplechase runner, teamed up a year ago. Dunkerly feels he's made a lot of progress in the 5K since that union.
"This is the first year I've actually, seriously trained for the 5K, so I think it's what I'm going to focus on more in the future," Dunkerley said. "Josh is an all-American in the steeplechase so training with someone like Josh, he's pushing me constantly in every workout we do. It makes you get better."
McLachlan's bronze in the 100 was her second after also finishing third in the 200. Just 19, McLachlan has set her sights on the 2016 Paralympics in Rio de Janeiro, Brazil.
"I'm more than happy with bronze just to have another chance to stand on that podium," McLachlan said. "As soon as I get back, I'm going to start training for Rio. I want a different (medal) colour at Rio. I want to hear our anthem at Rio."
Elsewhere Friday, Canada's wheelchair rugby team edged Sweden 53-52 to advance to Saturday's semifinal. Canada will face defending champion U.S. with a berth in Sunday's championship game on the line.
The wheelchair basketball team takes on defending champion Australia for gold Saturday.