Norris, was born in 1861 in York Township, Sandusky County, Ohio and was the eleventh child of poor uneducated, unchurched farmers of Scotch-Irish and Pennsylvania Dutch descent. He graduated from Baldwin University and took a LL.B. degree in 1883 at the law school of Valparaiso University. He moved to a prosperous town in Nebraska, Beaver City, to practice law. In 1889 he married Pluma Lashley, who died in 1901; they had three daughters. He married Ellie Leonard in 1903; they had no children.

Norris relocated to the larger town of McCook, Nebraska in 1900, where he became active in local politics. He was elected to Congress as a Republican in 1902, with railroad support. He broke with them in 1906 and supported Theodore Roosevelt's plans to regulate rates for the benefit of shippers, such as the merchants who lived in his district. A prominent insurgent after 1908 he led the revolt against Speaker Joseph G. Cannon in 1910. By a vote of 191 to 156 created a new system in which seniority would automatically move members ahead, not the wishes of the leadership.

In January 1911 he helped create The National Progressive Republican League and was its vice president. He originally supported Robert La Follette, Sr. for the 1912 nomination, then switched to Roosevelt. He refused to bolt the convention and join Roosevelt's Progressive Party and instead ran for the Senate as a Republican, and was elected by the legislature. As a leading Progressive Republican Norris supported the direct election of senators and also the conversion of all state legislatures to the unicameral system, which was eventually implemented in 1934 in Nebraska.

Norris supported some of Wilson's programs but became a die-hard isolationist who feared bankers were manipulating the country into war. In the face of enormous pressure from the media and the administration, Norris was one of only six senators to vote against the declaration of war on Germany in 1917. He joined the "irreconcilables" who vehemently opposed and defeated the Versailles Treaty and the League of Nations in 1919.

Seniority brought him the chairmanship of the Agriculture and Forestry and the Judiciary committees. Norris was a leader of the Farm Bloc, advocated the rights of labor, and proposed to abolish the electoral college. He failed on these issues in the 1920s, but did block Henry Ford's proposals to modernize the Tennessee Valley. That was a project the government should handle, he insisted. Although a nominal Republican (which was essential to his seniority) he routinely attacked and voted against the Republican administrations of Harding, Coolidge, and Hoover. Norris supported Democrats Al Smith in 1928 and Franklin Roosevelt in 1932. Republicans regulars called him one of the "sons of the wild jackass."

In 1932, along with Rep. Fiorello LaGuardia (R-NY), Norris secured passage of the Norris-LaGuardia Act, which outlawed the practice of requring prospective employees not to join a labor union as a condition of employment (the so-called Yellow Dog Contract) and greatly limited the use of court injunctions against strikes.

As staunch supporter of the President Roosevelt's New Deal programs, Norris sponsored the Tennessee Valley Authority Act of 1933. In appreciation, the TVA Norris Dam and a new planned city in Tennessee were named after him. Norris was also the prime Senate mover behind the Rural Electrification Act of 1936 that brought electrical service to underserved and nonserved rural areas across the United States.

Norris left the GOP in 1936 (since seniority in the minority party was useless, and the Democrats offered him chairmanships) and was re-elected to the Senate as an Independent with Democratic Party support in 1936.

Norris opposed Roosevelt's plan to pack the Supreme Court, and railed against corrupt patronage. He was a half-hearted isolationist in from 1939 until 1941. Unable to secure Democratic support in the state in 1942, he was defeated by Republican Kenneth S. Wherry.