He became blind as a child but did not give up his dream of becoming a senator. In 1907, he was elected to the Senate as one of the first two senators from the new state of Oklahoma. He was re-elected in 1908 and 1914 but defeated in 1920. He was known as a member of the progressive wing of the Democratic Party, who worked with Republicans such as Robert La Follette. He was to a large extent no different from any other politician because of his blindness, but there were problems, as La Follette recounts an example in his memoirs when, during a filibuster, Gore did not realize that the senator who was to take over speaking for him had left the room, and the filibuster failed because he did not continue to speak.

He is also noted as being the author of a bill placed before the United States Senate during the early stages of World War I which encouraged American citizens not to travel aboard belligerent merchant vessels. The merchant vessels were under threat of attack by German U-boats, and the Senator felt the loss of American lives upon these boats threatened official American neutrality at the time.

Gore was re-elected in 1930 to the Senate. When Franklin D. Roosevelt first took office as President, Gore at first supported his New Deal but later feuded with him. After Gore retired from the US Senate in January, 1937, he practiced law in Washington, D.C., until his death on March 16, 1949. Gore was initially burried at Rosehill Cemetery, Oklahoma City, Oklahoma, but was later reinterred on July 19, 1949, in Fairlawn Cemetery, also in Oklahoma City.

He married Nina Belle Kay, a Texas plantation owner's daughter, in 1900. They had two children, Nina Gore (1903-1978), the mother of Gore Vidal and Thomas Notley Gore (1910-).

A major road artery in Lawton, Oklahoma, is named after him.