Post was born at North Hempstead, Long Island on February 19, 1766.

During the 1788 doctor's riot, he was attacked by a mob of angry citizens, only to be saved by the intervention of mayor James Duane.

In 1790, he married Mary Magdalen Bayley, daughter of Richard Bayley and sister of Elizabeth Ann Seton (later known as Mother Seton, and the first native-born citizen of the United States to be declared a saint).

He visited the celebrated schools of Europe, and returned in 1793 with a splendid anatomical cabinet.

Post was one of the pioneers among American surgeons, and was long remembered as a successful operator, especially in the ligation of vital arteries.