William Mathews Blackford was born on August 19, 1801, at Catoctin Furnace in Frederick County, Maryland, the third of four sons and fourth of six children of Benjamin Blackford and Isabella Arthur Blackford. He grew up there and in Shenandoah County, where his father owned and operated a large and profitable ironworks. By 1824 Blackford had qualified as an attorney, and in January 1825 he moved to Fredericksburg and began to practice law. On October 12, 1825, he married Mary Berkeley Minor in Caroline County. They had two daughters and six sons.
In addition to his law practice, Blackford acted as an agent for several years for the Mutual Assurance Society of Virginia. In 1828 he bought the Fredericksburg Political Arena and Literary Messenger from his brother-in-law and plunged into the presidential campaign on behalf of President John Quincy Adams. Blackford owned and edited the Political Arena until October 1841 and consistently and vigorously supported the Whig Party. Blackford and his wife were both active in the Episcopal Church, in the temperance movement, and in Fredericksburg auxiliaries of the American Colonization Society, which they were instrumental in founding and running.
On February 10, 1842, Presidentappointed Blackford chargé d’affaires to New Granada. Blackford and his son lived in Bogotá for almost three years while he tried to settle the long-standing American claims against New Granada resulting from seizures of ships and cargoes during the South American wars for independence. Blackford soon concluded that he would have as little success as his predecessors unless the United States imposed a naval blockade. He turned his attention to negotiating a postal convention, which was signed on March 6, 1844, and ratified on December 20. Blackford also negotiated a commercial treaty between New Granada and the United States, but because the treaty did not end discriminatory duties, the United States Senate never ratified it. While in New Granada Blackford also kept a watchful eye on French and British attempts to secure exclusive rights to construct a railroad or a canal across the Isthmus of Panama.
Blackford returned to the United States on February 12, 1845, after the Democratic Party won the presidential election of 1844, and he resigned as chargé d’affaires effective May 13, 1845. In March 1846 he bought a controlling interest in, and became the editor of, the Lynchburg Virginian, the most influential Whig newspaper in Piedmont Virginia. Blackford sold his interest in the Virginian in 1850 when he was appointed postmaster of Lynchburg. After the Democratic Party took over the presidency in 1853, Blackford lost his job as postmaster, and on May 4, 1853, he became cashier of the new Exchange Bank of Lynchburg. He remained cashier until his death.
Blackford opposed secession in 1861 but after the fact became a firm supporter of the Confederacy. Five of his sons fought in the Confederate army, he opened his home toConfederate soldiers, and after the he raised $4,000 for the citizens of his old hometown. Blackford was an early admirer of and served as an escort when his body passed through Lynchburg. In June 1863 Blackford accepted the position of Confederate States Treasury agent in Lynchburg. Blackford died at his Lynchburg home during the night of 14–15 April 1864 and was buried in Spring Hill Cemetery there.