The body of Justice Teori Zavascki was recovered from the wreckage of a small plane that crashed near the coastal town of Paraty, off the coast of Rio de Janeiro state, state firefighters said.
Two other bodies that have not been identified were also found at the crash scene.
The death was confirmed via Facebook by the 68-year-old judge's son Francisco Prehn Zavascki.
"Dear friends, we just received the confirmation that my father passed away! Thank you all for your support," Prehn Zavascki posted.
Teori Zavascki's plane had left Sao Paulo's Campo de Marte airport around 1 p.m. local time (10 a.m. ET). Less than one hour later, the plane crashed. According to the Brazilian National Air Force, the plane was owned by hotel mogul Carlos Alberto Filgueiras.
The late Justice, who was appointed to the Supreme Court by former President Dilma Rousseff in 2012, was in charge of the probe known as Lava Jato, or Car Wash, the massive kickback and corruption scheme involving many of Brazil's biggest companies, including state-run oil giant Petrobras.
His death will likely raise concerns about how the investigation will proceed. Zavascki was widely seen as an impartial figure in a case that has shaken Brazil's political class to its core.
It is unclear what will happen with the judge's case load now. According to the court's regulations, in the event of death, pending investigations should be assigned to the justice replacing the one who passed away. Another article in the internal rules states that the president of the court may reassign the case to a sitting judge under exceptional circumstances.
In order to name a new justice, President Michel Temer would have to nominate someone who would have to be vetted by the Senate's Constitutional Justice Commission and approved by the full chamber.
Speaking from the presidential palace, Temer declared three days of mourning and called Zavascki's death a "painful occurrence."
"At this moment of grief, I would like to express our condolences to the family of the justice and the rest of the people on the flight. I join all Brazilians in lamenting the loss of this public man, whose impeccable trajectory in favor of law and justice always stood him apart," Temer said.
Zavascki was born in 1948 in the city of Faxinal dos Guedes, in Santa Catarina state. He served as the Brazilian Central Bank's council from 1976-1989. He later became a judge and was on the bench of the Superior Justice Tribunal, the country's second most important court, from 2003 to 2012.