His passing was announced on Sunday by the Hoover Institution at Stanford University, where Shultz had worked for more than three decades, reports Xinhua news agency.
He died at his home in California. The cause of his passing was not mentioned.
“Our colleague was a great American statesman and a true patriot in every sense of the word. He will be remembered in history as a man who made the world a better place,” Condoleezza Rice, a former Secretary of State and current Director of the Hoover Institution, said in a statement issued by the Institution.
Shultz is one of the only two Americans to have held four different federal cabinet-level positions.
He served as Secretary of Labour, Director of the Office of Management and Budget, and Secretary of the Treasury in the Richard Nixon administration.
He was Secretary of State in the Reagan era from 1982 to 1989.
His work in presidential administrations extended back to President Dwight D. Eisenhower, when Shultz worked as a senior staff economist on his Council of Economic Advisers during the 1950s.
He was awarded the Presidential Medal of Freedom in 1989.
He played a crucial role in negotiating the Intermediate-Range Nuclear Forces Treaty between Washington and Moscow, which leaders of both sides signed in 1987.
Born in New York City in December 1920, Shultz graduated from Princeton University before serving in the US Marine Corps in World War II.
He later earned a Ph.D. in industrial economics in 1949 from the Massachusetts Institute of Technology.
In a statement on Sunday evening, President Joe Biden called Shultz a “gentleman of honour and ideas”.
“I regret that, as President, I will not be able to benefit from his wisdom, as have so many of my predecessors.
“And, while he and I sometimes argued the opposite sides of issues when I was a young senator, I was proud to often find common ground on issues vital to the security and prosperity of the American people,” Biden added.
Incumbent Secretary of State Antony Blinken called Shultz a “legend” and a “visionary”, noting that he “urged serious action on the climate crisis at a time when too few leaders took that position”.
House Speaker Nancy Pelosi, a long-time friend of Shultz’s, said ithat with his passing, “the world has lost a revered statesman and brilliant public servant”.