Pierson was born in Morristown, New Jersey and was raised as a religious perfectionist Presbyterian, believing in God's direct interaction in the world in correlation to individual or collective sins.
He remained unmarried, working on Pearl Street as a merchant, until 1822 when he met Sarah Stanford.
The two were married and became heavily involved in mission work on Bowery Hill and Five Points, rejecting Yankee Presbyterian in favor of egalitarianism and retrenchment.
After eight years of marriage, Sarah died from what was reported as overwork, causing major her husband's mental health.
Robert Matthews was accused of poisoning Pierson and the case became extremely popular in the local penny presses.