Short was the adopted son (or possibly protégé) of President Thomas Jefferson. He was born into a well-to-do planter family in Virginia.
He helped found the US academic honor society Phi Beta Kappa, served his father as secretary in France and as later as chargé d'affaires; and was US diplomat to Russia, Spain and the Netherlands until 1810. He was also a member of the Virginia Council of State. After retiring from the diplomatic service he became a very wealthy landowner.