After studying botany at the University of Nebraska and law at Harvard (1889–90), Pound was admitted to the Nebraska bar, and he practiced law while also teaching at the state university (1890–1903). While serving as director of the state botanical survey (1892–1903), he discovered a rare lichen, which was subsequently named Roscopoundia.

Pound also served as commissioner of appeals for the state supreme court (1901–03) and commissioner on uniform state laws for Nebraska (1904–07). He taught at Northwestern University in Evanston, Illinois (1907–09), and at the University of Chicago (1909–10), after which he went to Harvard, where he was professor of law (1910–37) and dean of the law school (1916–36). On his resignation as dean, he received a “roving professorship” there and taught a variety of subjects until his retirement (1947). After World War II he spent some time in China reorganizing the Nationalist Chinese judicial system.

Pound's five-volume Jurisprudence is among the most comprehensive of 20th-century legal works. His theory of sociological jurisprudence required that inherited legal codes and traditions be adjusted to reflect contemporary social conditions. The theory may have partially inspired—and was advanced by others as a justification of—the New Deal legislation of President Franklin D. Roosevelt (Roosevelt, Franklin D.) in the 1930s, which Pound nonetheless considered extreme.