Bankhead was born on April 12, 1874 at the Bankhead plantation in Lamar County, Alabama, the second son and fourth of five children of John Hollis Bankhead and Tallulah James (Brockman) Bankhead. He came of a political family. His father served as a Congressman and later Senator from Alabama; his older brother, John Hollis Bankhead II, was Senator from Alabama from 1930 until his death in 1946.
Young William attended country schools, was graduated from the University of Alabama in 1893, and received a law degree from Georgetown University, Washington, D. C. , in 1895.
He began the practice of law that fall in Huntsville, Madison County, Alabama, but soon moved to New York City. He was eager to become an actor, but his parents vigorously opposed his wishes. While in New York he joined Tammany Hall and worked in the 1897 mayoralty campaign of Robert Van Wyck. After returning to Huntsville at the urging of his family, he immediately became active in politics. He was representative for Madison County in the state legislature of 1900-01 and city attorney of Huntsville, 1898-1902. Moving to Jasper, Alabama, in 1905, he served as solicitor of the 14th state judicial circuit, 1910-14.
Bankhead's first race for Congress, in 1914, was unsuccessful. The conservative faction of the Alabama Democratic party, however, in which his father and Oscar W. Underwood were leading figures, generally held the upper hand, and in 1916 Bankhead was elected from the newly created 10th congressional district, defeating Admiral Richmond Pearson Hobson. Thereafter he served continuously in the House until his death.
In 1934 he was elected majority leader of the House, though he was ill with heart trouble much of the time until 1936. When Speaker Joseph W. Byrns of Tennessee died in that year, Bankhead was elected to succeed him.
In 1940 he was chosen to make the keynote address at the Democratic National Convention. As a measure of his popularity, those delegates hoping to block the vice-presidential nomination of Henry A. Wallace - Roosevelt's own choice for a running-mate-rallied behind Bankhead, giving him 329 votes on the first and only ballot. A few weeks later, against the advice of his physician, Bankhead went to Baltimore to address a party rally. Stricken at his hotel before he could make his speech, he was moved to the Naval Hospital at Bethesda, where he died three weeks later. Though he had suffered from heart trouble and sciatica, the immediate cause of death was a rupture of an artery in the abdomen. A funeral service held for him in the House of Representatives was attended by President Roosevelt and other leading officials. He was buried in Oak Hill Cemetery, Jasper, Alabama.
Although he gave strong support to the program of President Franklin D. Roosevelt and described himself as a New Dealer, Bankhead personally believed in more conservative government; as Congressman Adolph J. Sabath of Illinois observed, he was a "New Dealer by adoption. "
Bankhead was a tall, handsome man and a fluent speaker. As a Congressman Bankhead was known as a loyal party man. A conciliator, not a combatant, he made friends easily and worked well with his fellow members.
In 1900 Bankhead married Adalaide Eugene Sledge of Memphis, by whom he had two daughters, Evelyn Eugenia and Tallulah Brockman. Tallulah, who inherited her father's interest in the stage, became a famous actress. Mrs. Bankhead having died three weeks after the birth of Tallulah in 1903, Bankhead in 1915 married Florence McGuire of Jasper.
