De Leon was the Socialist Labor candidate for governor of New York in 1891, and for years he edited the Socialist Labor weekly, The People. He was an inflexible and doctrinaire Marxian revolutionist and consequently fell out with most other liberal leaders. He opposed unionization of labor according to trades and led the group that formed the Socialist Trade and Labor Alliance, but his leadership was too radical for some of the members (prominent among them Morris Hillquit), who withdrew in 1899 and ultimately formed the Socialist party.

De Leon's prestige subsequently lessened. He helped to found the Industrial Workers of the World in 1905, but in the quarrel over political action he and his followers were expelled. The rival Workers' International Industrial Union, which he then organized, did not flourish. He wrote a great deal of Socialist polemical literature and translated a work of Karl Marx.