On August 8, 1854, James Paul Clarke was born in Yazoo City, Mississippi. Educated in the public schools and at Professor Tutwilder's Academy, Greenbrier, Alabama, he was admitted to the bar in 1879, one year after his graduation from the University of Virginia Law School. The same year he moved to Arkansas, where he opened a practice in Helena, Phillips County. A member of the state House of Representatives from 1886 to 1888, Clarke went on to serve in the state Senate until 1892. He was the president of that body in 1891 and ex officio lieutenant governor. Clarke maintained his participation in politics as attorney general of Arkansas from 1892 to 1894 and as governor of Arkansas from 1895 to 1896. Declining renomination, Clarke moved in 1897 to Little Rock, Arkansas, where he resumed his law practice.

Six years later, he was elected to the U.S. Senate and served until his death. Known for his "unqualified independence," he broke with his party in its opposition to President Theodore Roosevelt's policy on the Panama Canal. President Roosevelt, in fact, largely attributed the passage of the canal bill to him. Clark was ardently in favor of Philippine independence. He supported employers' liability and workmen's compensation legislation and opposed literacy tests for immigrants.

He was elected president pro tempore of the Senate in 1913 and again in 1915. He was also a member of the Democratic National Committee. James Clarke died in Little Rock, Arkansas, on October 1, 1916.