Sheppard studied at the University of Texas at Austin, earning a law degree in 1897. After attending Yale University, he began practicing law with his father in Pittsburg, Texas and later Texarkana.

In 1902, Morris Sheppard was elected as a Democrat to replace his deceased father in the House of Representatives. He held this seat until his resignation in 1913, when he succeeded in his bid to fill a vacancy in the Senate. During his tenure, he was a vocal supporter of the temperance movement. He helped write the Webb-Kenyon Act (1913) to regulate the interstate shipment of alcoholic beverages, authored the Sheppard Bill (1916) to impose prohibition on the District of Columbia, introduced the Senate resolution for the Eighteenth Amendment establishing national prohibition, and helped write the Volstead Act which provided for its enforcement. Sheppard held his seat until his death in Washington, D.C. in 1941, serving as Democratic whip between 1929 and 1933.

Sheppard is perhaps best known for asserting that "There is as much chance of repealing the eighteenth amendment as there is for a hummingbird to fly to the planet Mars with the Washington Monument tied to its tail."

Sheppard's wife, Lucille Sanderson, married the other Texas senator, Tom Connally, the year after Sheppard's death . Sheppard and his wife were the grandparents of Connie Mack III, U.S. Senator from Florida, and great-grandparents of Connie Mack IV, U.S. Representative from Florida.

Future U.S. President and then-representative Lyndon Johnson ran unsuccessfully for Sheppard's Senate seat in the special election caused by his death in 1941.

This article incorporates facts obtained from the public domain Biographical Directory of the United States Congress.