Brookhart, a Republican first took office as a United States Senator, representing Iowa, on November 7, 1922 to complete the term of William S. Kenyon, who resigned from office. In his first attempt at election to a full term, Brookhart appeared to have defeated Daniel F. Steck in the 1924 election by a small margin, with Brookhart getting 447,594 votes to Steck's 446,840. Brookhart took office on March 4, 1925 and served until April 12, 1926 when the Senate voted by a margin of 45 to 41 to replace him with Steck, who served out the remainder of the term. On other occasions the Senate has settled election disputes before a Senator took office, but this is the only time the results were overturned after the Senator was seated.
Brookhart successfully ran for Iowa's other Senate seat in 1926. He served a full six year term, but was unsuccessful for the Republican nomination in 1932.
Brookhart was president of the National Rifle Association from 1921 to 1925. He served in the U.S. Army during the Spanish American War and World War I, where he reached the rank of lieutenant colonel.