Chapman was born on September 26, 1774, in Leominster, Massachusetts, the second child of Nathaniel and Elizabeth Chapman (née Simonds, married February 8, 1770). His birthplace has a granite marker, and the street is now called Johnny Appleseed Lane. Chapman's mother, Elizabeth, died in 1776, shortly after giving birth to a second son, Nathaniel Jr., who died a few days later. In 1780, his father, Nathaniel, who was in the military, returned to Longmeadow, Massachusetts, where, in the summer of the same year, he married Lucy Cooley.
Author Rosella Rice stated, "Johnny had one sister, Persis Broom, of Indiana. She was not at all like him; a very ordinary woman, talkative, and free in her frequent, 'says she's' and 'says I's.'"
According to some accounts, an 18-year-old John persuaded his 11-year-old half-brother Nathaniel Cooley Chapman to go west with him in 1792. The duo apparently lived a nomadic life until their father brought his large family west in 1805 and met up with them in Ohio. The younger Nathaniel decided to stay and help their father farm the land.
Shortly after the brothers parted ways, John began his apprenticeship as an orchardist under a Mr. Crawford, who grew apples, thus inspiring Chapman's life journey of planting apple trees. In 1800, at the age of 26, Chapman was in Licking River, Ohio. His first orchard was on the farm of Isaac Stadden in Licking County. In 1806, he embarked upon a canoe voyage down the Ohio, Muskingum, and Walhonding rivers, using two canoes lashed together to transport himself and his seeds.