Inouye, a senator since January 1963, was currently the longest serving senator and was president pro tempore of the Senate, third in the line presidential succession. His office said Monday that he died of respiratory complications at a Washington-area hospital.
Senate Majority Leader Harry Reid announced Inouye's death on the Senate floor.
Inouye was a World War II hero and Medal of Honor winner who lost an arm to a German hand grenade during a battle in Italy. He became the first Japanese-American to serve in Congress, when he was elected to the House in 1959, the year Hawaii became a state. He won election to the Senate three years later and served there longer than anyone in American history except Robert Byrd of West Virginia, who died in 2010 after 51 years in the Senate.
After Byrd's death, Inouye became president pro tem of the Senate, a largely ceremonial post that also placed him in the line of succession to the presidency, after the vice president and the speaker of the House.
Although tremendously popular in his home state, Inouye actively avoided the national spotlight until he was thrust into it. He was the keynote speaker at the 1968 Democratic National Convention, and later reluctantly joined the Senate's select committee on the Watergate scandal. The panel's investigation led to the resignation of President Richard Nixon.
Inouye also served as chairman of the committee that investigated the Iran-Contra arms and money affair, which rocked Ronald Reagan's presidency.
A quiet but powerful lawmaker, Inouye ran for Senate majority leader several times without success. He gained power as a member of the Senate Appropriations Committee and chairman of the defense appropriations subcommittee before Republicans took control of the Senate in 1994.
When the Democrats regained control in the 2006 elections, Inouye became chairman of the Senate Commerce Committee. He left that post two years later to become chairman of the powerful Senate Appropriations Committee.
Inouye also chaired the Senate Indian Affairs Committee for many years. He was made an honorary member of the Navajo nation and given the name "The Leader Who Has Returned With a Plan."
In 2000, Inouye was one of 22 Asian-American World War II veterans who belatedly received the nation's top honor for bravery on the battlefield, the Medal of Honor. The junior senator from Hawaii at the time, Daniel Akaka, had worked for years to get officials to review records to determine if some soldiers had been denied the honor because of racial bias.