Blackburn was born about May 1761 in Frederick County, the youngest of nine sons and two daughters of Benjamin Blackburn and Mary Blackburn. The family moved to Virginia from Pennsylvania well before Blackburn’s birth, migrated to Augusta County in 1774, and subsequently moved to western North Carolina. Blackburn probably intended to go into the Presbyterian ministry when he entered Liberty Hall Academy (now Washington and Lee University). A brief interval of service in the army during the closing months of the Revolutionary War interrupted his education, but he received an AB from Liberty Hall in 1785. On August 18 of that year Blackburn married Ann Mathews, a daughter of George Mathews. Apparently accompanied by the newlyweds, Mathews soon moved from Staunton to Georgia, where he had begun acquiring land in Wilkes County in March 1784. Blackburn and his wife had no children of their own but adopted a son who died young.
In Georgia Blackburn became rector of an academy at Washington in Wilkes County and prepared himself for the legal profession. Aided no doubt by the political eminence of his father-in-law, who served as governor of Georgia from 1787 to 1788 and 1793 to 1796, Blackburn became a general in the militia and won election to the Georgia State Senate, representing Elbert County from 1791 to 1795. During the 1794–1795 session Blackburn was accused of helping to gain legislative passage of the infamous Yazoo land bill, which granted approximately 50 million acres west of the Chattahoochee River to four companies for $500,000. His father-in-law, then serving his second term as governor, had been granting land liberally in order to settle Georgia’s undeveloped frontier. Unlike some of his predecessors, however, Mathews had awarded vast tracts to a few speculators and corrupt politicians and signed the bill. No wrongdoing was proved on the part of either the governor or Blackburn, but the widely circulated accusations made Blackburn very unpopular.
In disgust Blackburn returned to Virginia by May 1796, bringing nineteen slaves with him. He immediately purchased a tract of land in Bath County, part of an estate named Cloverdale. Blackburn built a house there that became known as the Wilderness Farm. On November 8 and 15, 1796, Blackford qualified to practice law in Bath and Augusta counties. He lived in Bath County for the rest of his life. In 1805 Blackburn contracted to purchase another 1,734 acres of the original 2,080-acre Cloverdale tract but did not take legal possession until 1815 after litigation settled ownership of the property. With these purchases Blackburn brought his total landholdings to 2,173 acres.
General Blackburn, as he was usually called, became an extremely successful attorney at a time when the bar in that part of Virginia was one of the most distinguished and competitive in the state. His speeches in court, sometimes eloquent, sometimes humorous, and sometimes bitterly sarcastic, became legendary. Blackburn became one of the wealthiest men in Bath County. At the time of his death the value of his total estate in Bath and Augusta counties probably exceeded $140,000.
In politics Blackburn was a Federalist, and he may have continued to regard himself as one even after the party ceased to exist. He represented Bath County in the House of Delegates during the assemblies of 1799–1801, 1809–1811, 1812–1813, 1816–1818, 1820–1822, 1823–1824, and 1825–1826. In 1811 and 1813 he lost congressional elections to William McCoy, a, and he also ran unsuccessfully for the Virginia Convention of 1829–1830. As competitive and vocally opinionated in politics as in court, Blackburn became notorious for what one acquaintance described as his “strong abusive denunciations of the Republicans.” His speeches as printed in pamphlets and extracted in newspapers employed a debating style that was vigorous, partisan, learned, and often eloquent. One nineteenth-century writer credited Blackburn with drafting the first antidueling law in Virginia, adopted in January 1810, although the legislative records contain no corroborative evidence. In 1819 he served as a commissioner from Virginia to consult with representatives of other states interested in opening transportation links between the East Coast and the Ohio River and in removing obstructions to the navigation of the Ohio. Blackburn submitted a long report on the subject to the General Assembly in December of that year.
Blackburn served as a trustee of his alma mater, which became known as Washington Academy, then Washington College, from January 31, 1797, until July 19, 1830. At the time of his death he owned forty-six slaves and stipulated in his will that if they would agree to immigrate to Liberia, he would manumit them and pay their travel expenses. All but two took advantage of the opportunity to gain freedom. Blackburn died at his Wilderness plantation on March 2, 1835. His widow had his body buried in the churchyard of Trinity Episcopal Church in Staunton and erected a monument over his grave.