Wallace was born on a farm near Orient, Adair County, Iowa, and graduated from Iowa State College at Ames in 1910. He served on the editorial staff of Wallace's Farmer in Des Moines, Iowa from 1910 to 1924 and was editor from 1924 to 1929. He experimented with breeding high-yielding strains of corn (maize), and was the author of many publications on agriculture. In 1915 he devised the first corn-hog ratio charts indicating probable course of markets. The company he founded during this time is now known as Pioneer Hi-Bred, and is among the most profitable agriculture corporations in the United States today.
In 1933, Wallace was appointed United States Secretary of Agriculture in the Cabinet of President Franklin Delano Roosevelt. He served in this position until September 1940, when he resigned, having been nominated for Vice President. He was elected in November 1940 as Vice President on the Democratic ticket with President Franklin D. Roosevelt and was inaugurated January 20, 1941, for the term ending January 20, 1945.
Wallace was bumped from the Democratic ticket in 1944, largely due to party concerns over FDR's failing health and Wallace's perceived ultra-liberal viewpoints. The party would go on to nominate Missouri Senator Harry S Truman. Roosevelt placated Wallace by appointing him Secretary of Commerce, where Wallace served from March 1945 to September 1946.
Following his term as Secretary of Commerce, Wallace became the editor of The New Republic magazine, using his position to vociferously criticize Truman's foreign policy. He left that position in 1948 to make an unsuccessful run as a Progressive Party candidate in the 1948 U.S. presidential election.
Wallace resumed his farming interests, and was a resident of South Salem, New York. During his later years he was responsible for a number of advances in the field of agricultural science. Among his many accomplishments was a breed of chicken that at one point accounted for the overwhelming majority of all egg-laying chickens sold across the globe. He died in Danbury, Connecticut. His remains were cremated at Grace Cemetery in Bridgeport, Connecticut, and the ashes interred in Glendale Cemetery, Des Moines, Iowa.