Wythe was highly respected by his fellow Virginians. Thomas Jefferson wrote of him, "No man ever left behind him a character more venerated than George Wythe. His virtue was of the purest tint; his integrity inflexible, and his justice exact; of warm patriotism, and, devoted as he was to liberty, and the natural and equal rights of man, he might truly be called the Cato of his country."
George Wythe was a man of many accomplishments. He was Virginia's foremost classical scholar, dean of its lawyers, a Williamsburg alderman and mayor, a member of the House of Burgesses, and house clerk. He was the colony's attorney general, a delegate to the Continental Congress, speaker of the state assembly, the nation's first college law professor, Virginia's chancellor, and a framer of the federal Constitution. As the first professor of law at the College of William and Mary, those who studied and worked under him were the future Supreme Court Justice John Marshall, presidents Thomas Jefferson and James Monroe, and the statesman Henry Clay.
Wythe was one of the country's earliest abolitionists and freed his slaves. Late in his life, Wythe freed all his slaves and provided them a means of support until they were able to support themselves.
He was poisoned - it is believed by his nephew who was trying to poison the slaves who were to inherit - and died after two weeks of suffering. In his final will, he left all of his books to Thomas Jefferson.