Appartenente al Partito Democratico, ha rappresentato a Washington lo Stato delle Hawaii sin dalla sua ammissione come 50º Stato (1959), dapprima in qualità di primo deputato alla Camera dei Rappresentanti, quindi come senatore dal 1963, venendo poi sempre rieletto fino alla morte, avvenuta nel 2012.
Giunto al suo ottavo mandato, dal 28 giugno 2010, in seguito alla morte del collega di partito Robert Byrd, egli è stato eletto Presidente pro tempore del Senato, in quanto membro da più tempo in carica.
È scomparso nel 2012 all'età di 88 anni a seguito di problemi respiratori[1].
«Second Lieutenant Daniel K. Inouye distinguished himself by extraordinary heroism in action on 21 April 1945, in the vicinity of San Terenzo, Italy. While attacking a defended ridge guarding an important road junction, Second Lieutenant Inouye skillfully directed his platoon through a hail of automatic weapon and small arms fire, in a swift enveloping movement that resulted in the capture of an artillery and mortar post and brought his men to within 40 yards of the hostile force. Emplaced in bunkers and rock formations, the enemy halted the advance with crossfire from three machine guns. With complete disregard for his personal safety, Second Lieutenant Inouye crawled up the treacherous slope to within five yards of the nearest machine gun and hurled two grenades, destroying the emplacement. Before the enemy could retaliate, he stood up and neutralized a second machine gun nest. Although wounded by a sniper’s bullet, he continued to engage other hostile positions at close range until an exploding grenade shattered his right arm. Despite the intense pain, he refused evacuation and continued to direct his platoon until enemy resistance was broken and his men were again deployed in defensive positions. In the attack, 25 enemy soldiers were killed and eight others captured. By his gallant, aggressive tactics and by his indomitable leadership, Second Lieutenant Inouye enabled his platoon to advance through formidable resistance, and was instrumental in the capture of the ridge. Second Lieutenant Inouye’s extraordinary heroism and devotion to duty are in keeping with the highest traditions of military service and reflect great credit on him, his unit, and the United States Army.»
— 21 giugno 2000
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