"President John Magufuli died of a heart ailment that he has battled for over 10 years," Samia Suluhu Hassan said.
Hassan is now the acting president of Tanzania. While a date for her swearing-in has not yet been announced, she will be Tanzania's first female president.
Magufuli was one of Africa's most prominent Covid skeptics.
Early on in the pandemic, Magufuli dismissed the seriousness of coronavirus in Tanzania, urging his citizens to "pray coronavirus away," believing the "satanic virus can't live in the body of Jesus Christ," and blaming the growing number of positive cases on faulty test kits.
In June, he claimed his country had eradicated coronavirus "by the grace of God," questioned the safety of foreign Covid-19 vaccines, and made no plan to procure any shots for his country, instead pushing for the use of herbal medicine and steam treatments.
Tanzania hasn't reported Covid-19 figures since April 2020, prompting the World Health Organization to call for Tanzania to publish data on the coronavirus and ramp up public health measures.
Last month, the US Embassy in Dar es Salaam warned that Covid-19 cases had been surging since January.
Known as "The Bulldozer" for his tough stance against corruption and for his hardline policies, Magufuli swept to victory in October 2015 as Tanzania's fifth president.
But excitement over Magufuli's intolerance for corruption was short-lived as he began a clampdown on democracy and critical voices.
Magufuli oversaw closures and suspensions of numerous media outlets, while his government undermined judicial and parliamentary independence, implemented a partial ban on public rallies, harassed MPs, closed online political space, and prosecuted critics under defamation and sedition laws.
In June 2017 Magufuli announced that pregnant students would not be allowed to return to school after giving birth.
"In my administration as the President no pregnant girl will go back to school... she has chosen that of kind life, let her take care of the child," he said at a public rally in 2017.
Tributes to a 'Pan-African leader'
As news of the president's death emerged, opposition leader, Zitto Kabwe offered his condolences to Magufuli's family. "This is an unprecedented moment for our United Republic of Tanzania, and one that will undoubtedly move us all in very personal ways," the leader of the ACT-Wazalendo party said in a statement. "My immediate thoughts are with Mama Janeth, and the whole family of our deceased President."
He also offered "blessings, courage and patience" for Hassan. "My fellow Tanzanians, let us continue to pray for patience and understanding. This is a moment to show our maturity and integrity as a nation," Kabwe added.
British Prime Minister Boris Johnson was one of the first world leaders to express their sympathy at the death of Magufuli. "My thoughts are with his loved ones and the people of Tanzania," he wrote in a post on Twitter.
Kenya's President Uhuru Kenyatta paid his respects to Magufuli in a televised address Thursday morning and declared a seven-day period of national mourning in Kenya.
"Africa and the world have lost an illustrious leader whose vision, passion, and immense leadership propelled the nation of Tanzania forward... in the passing on of President Magufuli, I have lost a friend, a colleague and a visionary ally whom I worked closely, particularly on our commitment to forging lasting bonds between Kenya and Tanzania," he said.