An avid drawer of cartoons as a child, he was determined to become a professional cartoonist.
So, aged 19, Mauricio left his small home town and moved to Sao Paulo, Brazil's largest city, to pursue his dream.
Intending to produce cartoons for a newspaper, he was instead repeatedly turned down. He was told that his work wasn't good enough.
But not a person to be deterred, the young Mauricio came up with a plan - he'd get a different job on a newspaper, while continuing to practise and improve his skills as a cartoonist in his spare time.
His thinking was that once he was more established at a paper, he'd then try again - and again - to get his cartoons accepted.
So despite the sight of blood making him feel faint, in 1954 Mauricio got a job as a crime reporter on one of Brazil's bestselling titles - Folha de Sao Paulo.
"Of course it was not the start I dreamed about, but we can not be picky when we are starting, and I had to do what they allowed me to do," says Mauricio, who is now 80 years old.
He had to wait five years before he got a cartoon accepted.
That first daily comic strip was about a dog who engaged in philosophical conversations. It was popular enough for Mauricio to be able to quit reporting, and become a full-time cartoonist.
Almost six decades later, Mauricio has sold more than one billion comics and books.
A household name in Brazil, his work is also translated and sold around the world.
In addition, his company - Mauricio de Sousa Productions (MSP) - produces animated films and theatre productions, runs a theme park, makes computer games and cuddly toys, and licenses his characters to hundreds of consumer products.
While Mauricio doesn't like to discuss money, he is a multi-millionaire many times over.
He is also a workaholic who still leads the business every day, and has no plans to retire. "I work whenever I'm awake," he says.
Mauricio's most popular cartoon character is a seven-year-old girl called Monica, who appeared for the first time in 1963.
Named after one of his daughters, the fictional Monica is a strong-minded child who leads a gang of friends.
As Monica's adventures gained a loyal readership, Mauricio says that thanks to his mother's advice he made sure that he focused on his business affairs as much as he did on his writing and drawing.
"Something my mother used to advise me was that if I wanted to become a cartoonist I should do my drawing in the morning, and manage the business in the afternoon," he says.
Mauricio also started to hire staff to assist him, and travelled around Brazil to sell his cartoons to other newspapers.
Within three years his cartoons were being published in no less than 400 Brazilian newspapers, and his earnings soared.
Today, Mauricio says that while the comics are his "calling card", most of the company's profits comes from licensed products. His characters can be found on everything from nappies to furniture, clothing, and food items.
It is this business acumen as much as Mauricio's cartoon drawing skills that have seen him compared with the late Walt Disney.
Yet as much as Mauricio has focused on his finances, he has also been honoured for his efforts to use his cartoons - which include no less than 200 different characters - to promote good causes.
Themes he has promoted include protecting the rainforests, anti-smoking, vaccinations, the need for clean water, tackling pollution, and fighting drugs.
This work has seen him receive an award from the Pan American Health Organization, the public health agency that operates in all 35 nations across North and South America.
Mauricio is also the holder of a Brazilian presidential medal of honour, and his Monica cartoon character was named a United Nations International Children's Emergency Fund (Unicef) ambassador in 2007.
The first ever fictional character to be given the title, she was chosen because of her positive influence on children and families.
Looking ahead, Mauricio says that while he has no plans to retire, he has held "occasional meetings" about the issue, "because I do not want all this work to be damaged by bad planning".
In running the company he is helped by two of his 10 children, who hold senior roles.
Eladio Toldeo, a Brazilian business consultant, says that while the eventual leadership transition will need to be handled well, "Mauricio's legacy will remain regardless of who is managing the company" and its 500 employees.
In the meantime, Mauricio says: "Holidays make me restless because I do not like the idea of being three or four days without creating something.
"I need to take as much as I can from my mind, and create books, comic strips and other products for children. It is not a material need, it is something else."
Follow The Boss series editor Will Smale on Twitter @WillSmale1
For someone who is often called "the Walt Disney of Brazil", Mauricio de Sousa is a very good example of why you shouldn't give up on your dreams after an initial rejection.