William Jay combined management of the family estate at Bedford, New York, with judicial service and reform writing. Appointed to the Westchester County court in 1818, he became its first judge in 1820 and remained on the bench into the early 1840s. Religious conviction informed his campaigns for temperance, peace and the abolition of slavery. He also edited a life of his father, John Jay, using family papers to explain the elder Jay's public career.

Jay helped establish the American Anti-Slavery Society in 1833 and served as its corresponding foreign secretary in 1835–1837. His Inquiry into the Character and Tendency of the American Colonization and American Anti-Slavery Societies rejected colonization as a substitute for freedom and equal rights. He also attacked federal policies protecting slavery, urging emancipation in the District of Columbia and the exclusion of slavery from federal territories. Differences within the movement led him to leave the society in 1840, but he continued writing against slavery.

International arbitration formed another sustained interest. His 1842 War and Peace proposed agreements for settling disputes without resort to arms. He opposed the Mexican War and examined its connection with territorial expansion and slaveholding interests. Jay died at Bedford in October 1858. Frederick Douglass later honored his antislavery work in a public eulogy, connecting it with the continuing struggle for Black freedom.