Senate Democratic Caucus Director Ford Porter said family members contacted Nesbitt's legislative staff to inform them of his death. Porter said Nesbitt was diagnosed last week with stomach cancer.
"Tonight, North Carolina lost a great leader, and I mourn a valued friend," said State Sen. Dan Blue, who replaced Nesbitt as Senate leader.
"Martin always believed in the people of our great state and strove to make North Carolina a better place. I have known and served with Martin for over thirty years and I will greatly miss his friendship, counsel, and candor," Blue said.
A statement from the state Democratic Party said North Carolina has lost a leader and champion of exemplary and distinguished public service.
Republican Senate President Phil Berger said Nesbitt "cared deeply about people and spent a lifetime fighting for what he believed would make North Carolina a better place. His passing leaves a deep void in our Senate family."
It was on Wednesday that a group of well-wishers lined a road near Interstate 40 to welcome the Asheville Democrat home. He arrived there in an ambulance.
Nesbitt, a Buncombe County native, was appointed to the House in 1979 to succeed his late mother, Rep. Mary Nesbitt.
Under the mentorship of four-term House Speaker Liston Ramsey, Nesbitt became a member of the so-called "Gang of Eight," a de facto committee of House and Senate Democrats that controlled the budget negotiations. He later became a chairman of the House Appropriations Committee under then-Speaker Dan Blue.
After being swept out of office in the 1994 Republican surge, Nesbitt returned to the House two years later and was appointed to the Senate in 2004. He became majority leader in 2009.
Nesbitt became minority leader in 2011 when Republicans took over the chamber.
Funeral arrangements are pending.