[5] On September 29, 1925, La Follette was elected as a Republican to the United States Senate to fill the vacancy caused by the death of his father.

He supported President Franklin D. Roosevelt and most New Deal legislation until he broke over the passage of the 1938 naval expansion bill.

Intimately tied with the very peculiar "progressive" Wisconsin political organization, who started as an Isolationist New Dealer and by degrees has turned into a confused anti-administration Nationalist.

He is a very eccentric and unpredictable political figure who continues to be radical in internal issues and obscurantist in foreign affairs.

He is entirely independent of business interests and pressure groups, and his strength comes from the traditional place occupied by his family in Wisconsin.

Being initially confident of victory, he further hurt his chances by staying on in Washington to draft and win passage of the Legislative Reorganization Act of 1946 rather than returning to Wisconsin to campaign for re-election.

[14] La Follette faced an aggressive campaign by McCarthy and failed to refute the latter's charges, several of which were false.

[17] In a Collier's Weekly article of February 8, 1947, La Follette reported infiltration of Communists onto Congressional committee staffs.

The only people he named were union leaders: Abram Flaxer of the UPWA, Reid Robinson of the MMSW, Ben Gold of the Furriers, Michael Quill of the TWU, and Joseph Ryan of the IL.

[18] In August 1947, Washington-based columnist Marquis Childs reported that La Follette was "comfortably established in his own offices in Washington as an economic consultant to several large corporations.

[20][21][22] On February 24, 1953, La Follette was found dead of a self-inflicted gunshot wound just days after his 58th birthday in Washington, D.C.[23] His aide Wilbur Voight stated he "apparently had been despondent over a lingering heart condition".

Some historians believe that La Follette killed himself out of fear of being exposed by McCarthy; others believe he succumbed to anxiety and depression that had plagued him for much of his life.