He was born as Kossola or Oluale Kossola, around 1840 in West Africa. Analyzing names and the other words attributed to the Africatown founders, historian Sylviane Diouf has concluded that he and many other members of the community belonged to what is now known as the Yoruba ethnic group, and lived in the Banté region of what is now Benin. His father was named Oluwale (or Oluale) and his mother Fondlolu; he had five full siblings and twelve half-siblings, the children of his father's other two wives. Interviewers Roche and Hurston, and those who used their work, referred to Lewis and his fellow-captives as "Tarkars." Diouf believes that the term "Tarkar" might have come from a misunderstanding of the name of a local king, or the name of a town.

During April or May 1860, Lewis was taken prisoner by the army of the Kingdom of Dahomey as part of its annual dry-season raids for slaves. Along with other captives, he was taken to the slaving port of Ouidah and sold to Captain William Foster of the Clotilda, a ship based in Mobile, Alabama, and owned by businessman Timothy Meaher. Although importation of enslaved persons into the United States had been illegal since 1808, Meaher may have believed that he could flout the law without consequences. Some reports suggest that breaking the law was part of Meaher's motivation for importing the slaves, as he reportedly bet a businessman $100,000 that he could circumvent the prohibition on transporting slaves. In a similar situation, the owners of the Wanderer, which had illegally brought a cargo of enslaved people to Georgia in 1858, were indicted and tried for piracy in the federal court in Savannah in May 1860 but acquitted in a jury trial. By the time the Clotilda reached the Mississippi coast in July 1860, government officials had been alerted to its activities, and Timothy Meaher, his brother Burns, and their associate John Dabney were charged with illegal possession of the captives. However, there was a gap of almost five months between the end of July 1860, when summonses and writs of seizure were issued against the Meahers and Dabney, and mid-December when they received them. During the intervening period the captives were dispersed and hidden, and without their physical presence as evidence the case was dismissed in January 1861.

Until the end of the Civil War (1861–65), Lewis and his fellows lived as de facto slaves of Meaher, his brothers, or their associates. Lewis was purchased by James Meaher, for whom he worked as a deckhand on a steamer. During this time he became known as "Cudjo Lewis." He later explained that he suggested "Cudjo," a day-name commonly given to boys born on a Monday, as an alternative to his given name when James Meaher had difficulty pronouncing "Kossola." Historian Diouf posits that the surname "Lewis" was a corruption of his father's name Oluale, sharing the "lu" sound; in his homeland, the closest analogue to what Americans understood as a surname would have been a patronymic.

During their time in slavery, Lewis and many of the other Clotilda captives were located at an area north of Mobile known as Magazine Point, the Plateau, or "Meaher's hammock," where the Meahers owned a mill and a shipyard. Although only three miles from the town of Mobile, it was isolated, separated from the city by a swamp and a forest, and easily accessible only by water. After the abolition of slavery and the end of the Civil War, the Clotilda captives tried to raise money to return to their homeland. The men worked in lumber mills and the women raised and sold produce, but these occupations did not allow them to acquire sufficient funds. After realizing that they would not be able to return to Africa, the group deputized Lewis to ask Timothy Meaher for a grant of land. When he refused, the members of the community continued to raise money and began to purchase land around Magazine Point. On September 30, 1872, Lewis bought about two acres of land in the Plateau area for $100.00.

Africatown developed as a self-contained community. The group appointed leaders to enforce communal norms derived from their shared African background, and developed institutions including a church, a school, and a cemetery. Diouf explains that Africatown was unique because it was both a "black town," inhabited exclusively by people of African ancestry, and an enclave of people born in another country. She writes, "Black towns were safe havens from racism, but African Town was a refuge from Americans.  Writing in 1914, Emma Langdon Roche noted that the surviving founders of Africatown preferred to speak in their own language among themselves. She described the English of adults as "very broken and not always intelligible even to those who have lived among them for many years." However, the residents also adopted some American customs, including Christianity. Lewis converted in 1869, joining a Baptist church.

During the mid-1860s Lewis established a common-law relationship with another Clotilda survivor, Abile (Americanized as "Celia"). They formally married on March 15, 1880, along with several other couples from Africatown. They remained together until Abile's death in 1905.

They had six children, five sons and a daughter, to each of whom they gave both an African name and an American name.Their eldest son, Aleck (or Elick) Iyadjemi, became a grocer; he brought his wife to live in a house on his father's land. Diouf describes this arrangement as a Yoruba-style "family compound." Another son, Cudjoe Feïchtan, was fatally shot by a sheriff's deputy in 1902. Lewis outlived all of his children as well as his wife. He allowed his daughter-in-law Mary Wood Lewis, his grandchildren, and eventually her second husband Joe Lewis (no relation) to remain in their house in the compound.

Lewis worked as a farmer and laborer until 1902, when his buggy was damaged and he was injured in a collision with a train in Mobile. As he was then unable to work, the community appointed him as sexton of the church. In 1903 it took the name of the Union Missionary Baptist Church.

Cudjo Lewis died July 17, 1935, and was buried at the Plateau Cemetery in Africatown. Since his death, his status as the last survivor of the Clotilda and the written record created by his interviewers have made him a public figure of the history of the community His legacy still exists. Although all of Cudjos' children past away it was Aleck, who was able to pass this great legacy on through children and those children had children who still carry on the tradition today In Cudjos' home of Mobile Alabama. People would have you believe they are descendants of Cudjo Lewis evryone wants to claim his pround African blood but we are the TRUE descendants of Cudjo and will continue to carry his torch. My name is Garry Lumbers and i am just doing what i was told to do!