It was the 38-year-old's 17th Paralympic gold medal and her ninth world-record swim of the week.
Hess, a mild cerebral palsy sufferer, was far too strong for her rivals as she cruised to victory in the S5 50m freestyle in 36.85secs.
Hess' success has now helped France to seventh place on the medals table with 26 golds behind leaders Australia with two days' competition remaining.
Comparisons
She is determined to be compared with Australian's swimming superstar Ian Thorpe.
"I want to be remembered in Paralympic history - you have Ian Thorpe, why not Beatrice Hess?" she said.
She claimed she wanted to repeat her six gold haul at the last Atlanta Paralympics not only to prove it was possible but also to dedicate her triumphs to her family.
"I wanted to do what I did in Atlanta because everybody says it's impossible; I want to show it's possible if you work hard," Hess said.
"I give the medals to my children and my brother-in-law, who has cancer. You need someone else to think about and to motivate you.
"I was scared that I wouldn't do it, because the standard is so high."
Hess could claim her seventh gold in Saturday's relay, but she said she would be satisfied with six.
With 17 gold, two silver and a bronze, she could retire after the Games a satisfied woman. But she is unsure of her future.
"I've sacrificed a lot, I want to look after my family first, then I will see if I will go on," she said.
American swimmer Curtis Lovejoy won his second gold capturing his fourth world record of the Games in the men's S2 50m freestyle for severely-disabled athletes, clocking 1m00.36s to lower his own world record, set in the heats.
Meanwhile, cerebral palsy sprinter Tim Sullivan won his fourth gold medal, pushing Australia to their 50th gold medal for the first time at a Paralympics.
The 25-year-old student won the T38 400m in a new world record of 50.30secs after also scoring in the 100m, 200m and 4x400m races.