Santini, who had never cooked professionally before she walked into the kitchen at the Mantova restaurant in 1974, will collect the award during this year's ceremony at the famous Guildhall in London on 29 April.
In 1996 the Italian chef became the first woman from the country to receive three Michelin stars - 22 years after she was first trained by Teresa, her new husband's grandmother.
Dal Pescatore was founded by the Santini family and remains a family business. Nadia's husband Antonio manages the front-of-house team, while sons Alberto and Giovanni also work for the business.
"I am very happy and honoured to receive this important recognition," said Santini of the award.
"For me it is for all at Dal Pescatore; for my family who work with me, my husband Antonio, my extraordinary sons Giovanni who runs the kitchen with me and Alberto who runs the room and takes care of the wine, for Antonio's mother who gave me many secrets and Valentina, Giovanni's wife who is also very active in the restaurant," she added.
The Veuve Clicquot World's Best Female Chef, inspired by the life and achievements of Madame Clicquot, is awarded to a chef who excites the 936 critics who voted in this category and who best represents the innovation, creativity and determination of the woman who set the standard for women in business.
This year marks the third time a female chef has been presented with this prestigious prize. In 2011 French chef Anne-Sophie Pic of Maison Pic in France beat Santini and Elena Arzak to the title - Arzak then scooped the prize last year.
Sophie-Pic was among the first to congratulate Santini on her achievement: "I have a great admiration for Nadia Santini," she said. "I appreciate her so much for her humility and her generosity.
"She is a role-model. I have identified myself tremendously with her: with her simplicity, her values, her honesty and emotional sensitivity," the French chef added.
Dal Pescatore is a mainstay on the World's 50 Best Restaurants having appeared in the top 50 eight times in the last 10 years. Angela Hartnett, chef-patron of Michelin-starred Italian restaurant Murano said Santini's family-run eatery provided each diner with a unique culinary experience.
"Nadia Santini is brilliant," she said. "Dal Pescatore is a fantastic restaurant; so relaxed and natural for a three star that you feel like you have been invited into their home."
Once again, BigHospitality will be reporting live from the awards at the Guildhall on 29 April. For all the latest from the event, including live coverage and exclusive interviews, keep checking the website, follow us on Twitter and like our Facebook page.