Kirchner had been ill in September, but was still a likely candidate in next year's presidential elections. He also served as secretary general of the South American alliance known as Unasur, as a congressman and as leader of the Peronist party.
The news shocked Argentines, who by law were staying at home Wednesday to be counted in the nation's census. Kirchner's supporters planned a mass gathering for Wednesday night outside the Casa Rosada, Argentina's presidential palace.
Kirchner worked hand-in-hand with his wife to mantain the ruling party's hold on power. Even more than Fernandez, he was seen as the heir to Argentina's strongman Juan Domingo Peron and one of the few people capable of managing Argentina's unruly and chaotic political scene.
With him gone, Fernandez is likely to face many new threats to her leadership.
"A great patriot has died," said Juan Carlos Dante Gullo, a ruling party congressman, to state TV. "This will leave a huge hole in Argentine politics. We will have to follow his example. Argentina has lost one of its greatest men."
"Our country needed this man so much. He was indispensable," she told radio Continental.
Kirchner served as president from 2003-2007, bringing Argentina out of severe economic crisis and encouraging judicial changes that set in motion dozens of human rights trials involving hundreds of dictatorship-era figures who had previously benefited from an amnesty.
As secretary general of the Union of South American Republics, or Unasur, Kirchner mediated one of the many recent disputes between Venezuela and Colombia. Both countries' leaders mourned his loss on Wednesday.
"It's a great loss for Argentina and a great loss for the continent," he said, adding that he would try to reach Fernandez to share his condolences.
Born in the Patagonian province of Santa Cruz, Kirchner and his wife were active in the Young Peronists party as students in La Plata, where he graduated in 1976. With the military firmly ruling the country, the young couple married and worked as private attorneys in the provincial capital, raising two children — Maximo and Florencia. After democracy returned in 1983, Kirchner entered public service, first as the provincial pensions chief, and then as mayor of Rio Gallegos.
In 1991, he became Santa Cruz's governor and Fernandez was elected to the provincial legislature, pushing through indefinite re-election and filling the provincial courts with sympathetic judges. In 1995 he was re-elected as governor by an overwhelming margin, laying the groundwork for a jump to politics at the national level.