Ezzidio was kidnapped as a small child and taken south to the Yoruba country. In 1827, while in his teens, he was sold to white slave traders who put him on a ship bound for Brazil. But the British navy's Africa squadron captured the ship and released the "recaptives", including young Ezzidio, at the city of Freetown. The young man now began a new life as the apprentice to Jean Billaud, a French shopkeeper. Billaud called the former slave "Isadore", which gradually became pronounced as "Ezzidio".
John Ezzidio, bright, resourceful, and ambitious, took easily to the world of commerce. He worked for Billaud for several years and, after the Frenchman died, found employment with other local merchants. Within ten years, Ezzidio had saved enough money to begin his own business. By 1841, he had purchased land and built a house. In 1844, he became an alderman on the city council; and in 1845, the mayor of Freetown.
Ezzidio was active in the Wesleyan Mission as a class leader and local preacher. In the 1850s, Rev. Thomas Dove, the mission superintendent, took Ezzidio to England where he made contacts with large wholesale firms from which he began to import goods directly, without going through middlemen. By the 1850s, Ezzidio had built up one of the largest and most prosperous businesses in the colony. In 1863, after a constitutional change established the Legislative Council, Ezzidio was elected an unofficial member of the colony's mercantile community, defeating a European candidate. He was the first African to serve on the council and, because the British soon abolished the elective principle, he was the only African to be elected until that principle was reintroduced in 1924. Ezzidio served on the council from 1863 until the eve of his death in 1872, holding the title of "Honourable".
The last years of Ezzidio's life were marked by a bitter feud with Rev. Benjamin Tregaskis, the new superintendent of the Wesleyan mission. Tregaskis, a man of dictatorial personality, opposed Ezzidio's influence in the mission and his approach to church policy.. The feud seems to have damaged both Ezzidio's health and his financial position. But John Ezzidio remains one of the outstanding success stories of early Freetown. He arrived on a slave ship — naked, penniless, and friendless — but rose ultimately to the heights of Sierra Leone society. His success came through faith, intelligence, determination and hard work.