Born in New York City, Gruening pursued a career in journalism after graduating from Harvard Medical School.

Gruening was born in New York City to a Jewish family,[2] the son of Phebe (Fridenberg) and Emil Gruening, a German-born eye and ear surgeon,[3] who had fought in the American Civil War, and was present when Confederate General Robert E. Lee signed the surrender which ended the war.

in which he outlined the ways in which the United States mirrored the actions of the British Empire in North America before the Revolutionary War in relation to the territory of Alaska.

A significant issue during Gruening's tenure as territorial governor, particularly in 1946, was a tuberculosis rate so high it caused him to declare a state of emergency.

Alaska spent one-tenth of its annual budget increasing awareness about TB, yet the death rate was still eight times the United States average.

[8] Another concern during Gruening's time as governor was the possible effect on wildlife caused by large numbers of soldiers arriving prior to the United States entry into World War II, and which would only increase during the conflict.

Gruening had been pushing for defense facilities in Alaska since his appointment to the governorship, and because of recent actions from Germany and Japan, Congress designated funds to build army forts and airfields in the territory.

Plans were made for blackouts and civilian defense forces, whose first assignment was "around-the-clock protection for radio stations, telephone exchanges, oil tanks, public utilities, and docks, and to be vigilant against possible sabotage.

"[5] The armed forces expanded their operations in Alaska, slowly moving toward the Aleutian Chain, the most accessible route from Asia.

The Japanese did reach Alaska in June 1942, bombing Dutch Harbor and landing on the islands of Attu and Kiska, the only continental U.S. locations captured in World War II.

[5] In connection with World War II but preceding U.S. involvement, Interior Secretary Harold L. Ickes developed a plan to resettle refugees fleeing the European continent in sparsely-populated Alaska.

After the 1964 Alaska earthquake, Gruening was part of the efforts to rebuild Anchorage, along with Representative Ralph Rivers, Governor Bill Egan and Senator Bob Bartlett.

Gruening's most notable act as an officeholder was being one of only two senators, along with Wayne Morse of Oregon, to vote against the Gulf of Tonkin Resolution which passed on August 7, 1964.

All our other issues and problems are slighted, impaired and unresolved until we halt the fighting, stop the... continuing drain of blood and treasure, and turn to the long-neglected and pressing needs at home.

In the article, Gruening notes that his 30-page speech, including exhibits, on March 10, 1964, was the first piece of opposition out of Congress regarding the Vietnam War.

"[14] However, Isaac Camacho, who became the first American to escape from a Viet Cong POW camp, said that whilst he was a prisoner, Gruening's anti-war rhetoric was used by his VC interrogators as propaganda.

His daughter, Caroline Gruening, enjoyed success in basketball, playing guard for Juneau-Douglas High School and Santa Clara University.

In 1977, Alaska donated a statue of Ernest Gruening to the United States Capitol's National Statuary Hall Collection.

Ernest Gruening Middle School in the Eagle River community of Anchorage, Alaska is named in his honor.