The following version of this book was used to create the guide: Charry, Brinda. The East Indian. Scribner, 2023.

In the Coromandel, a remote alluvial region of India, a young boy who goes by Tony lives with his amma, who makes her living as a prostitute. Tony's amma takes up a relationship with a wealthy white member of the East India Trading Company named Francis Day, and Tony spends his childhood with relative access to wealth as a result. When Tony's amma dies, Day sends him to London aboard a vessel piloted by his friend. The voyage goes poorly, and Day's friend dies, leaving Tony alone in London. He is taken in by Peter and Jane, who are from a different region of India, and begins working on the docks. He meets a girl named Mary Bengal with whom he develops a romance, and is planning to find passage back to India with her when he is kidnapped by a group of white traders along with several other young boys and sent across the Atlantic to the colony of Virginia.

When Tony arrives in Virginia, he is quickly made subject to indenture by a man named Menefie. The overseer, Ralph Ganter, is abusive toward Tony and his friends. When Ganter completes his indenture, Menefie transfers the bonds for Tony and his friends (Bristol, Cuffee, Dick, and Sammy) to Ganter and sends them up the James River to attempt to establish a homestead there. Ganter continues to treat them poorly, particularly the frail young Sammy. As soon as it has been completed, the farm is destroyed by a hurricane. On Christmas night, Tony has too much to drink and loses track of Sammy, leaving him alone with Ganter. It becomes clear that Sammy has been sexually abused, and he hangs himself shortly after.

In the wake of Sammy's death, Tony vows to kill Ganter, but before he can do so, Ganter forfeits his bond to Tony in a poker game and loses. Tony thus takes up with his new master, Archer Walsh, a gregarious adventurer who hopes to use Tony as an assistant in his travels. Walsh gives Tony much more freedom than Ganter and invites Tony to accompany him on a quest westward; word has arrived in the colony that the Earth is round and that there is a sea beyond the mountains that leads to India. Tony and Walsh head west and encounter a Monacan settlement where two boys, Shuren and Amoro, are dispatched to join them on their mission. While Tony, Shuren, and Amoro bathe in a creek one day in the Appalachian Mountains, Walsh is shot with an arrow by an unidentified assailant. Tony grieves Walsh's death and allows himself to be led back to the Monacan settlement by Shuren and Amoro.

Though Tony enjoys life with the Monacans, they trade him back to the Jamestown colonists in exchange for a captured Monacan boy. Tony is taken in by the local religious leader, Parson Blair, and begins receiving instruction in the Bible before being baptized. He reunites with his old friends, who are now working for a man named Adams alongside Ganter. Ganter, meanwhile, arrives at Blair's house to threaten to accuse Tony of murdering Walsh. One night, Tony is held up at knifepoint by a man named Noah Giles, who demands a cure for syphilis; Tony furnishes him with some "unicorn-horn powder" from his homeland. Giles begins making regular visits to Tony, which catches the attention of a local doctor, Joseph Herman, who confronts Tony and insists he stop selling false elixirs. Herman quickly has a change of heart, though, and offers to take Tony on as an apprentice. Tony joins Herman, but is disappointed when his responsibilities are more domestic than medicinal. He begins selling "love potions" behind Herman's back. When Herman finds out, he is tempted to let go of Tony, but the men reconcile and Herman begins teaching Tony more thoroughly about the art of healing.

Bristol and a white man named Martin begin organizing a rebellion against the masters, one that Cuffee and a boy named Flynn quickly become involved with. Dick, meanwhile, has become a favorite of the masters and is not let in on the plan. Meanwhile, a young boy named Sancho who works under Ganter's supervision begins complaining to Tony that Ganter is abusing him. Sancho's plight recalls Sammy to Tony's mind and he pledges to help Sancho avoid harm. Tony also becomes involved in a romantic relationship with a Black woman named Lydia. On the night of the rebellion, Tony is on his way to join his friends when Sancho summons him and informs him that Ganter has been wounded by Mad Marge, a mysterious figure who recurs throughout the novel. Tony arrives to care for Ganter and begins giving him excessive pain medication to prevent him from interfering with the rebellion. Tony murders Ganter by way of overdose, but his efforts are for naught; the rebellion is stopped by Dick, who turns his old friends in to the masters. Tony briefly stands trial for the murder of Ganter but is quickly acquitted. Bristol and Martin are found dead.

A disease begins sweeping through the colony that kills Lydia's master; her mistress begins accusing her of being a witch. Though Tony wants to stay with Herman and help treat the disease, he becomes increasingly concerned for Lydia's safety. Eventually, he elects for him and Lydia to join Cuffee and Flynn as they attempt to escape to Maryland. The quartet makes it some distance before Flynn is bit by a snake and they are forced to seek shelter with a local white family, who turns them in to the colonial authorities. Dick is sent to retrieve them and bring them back to the colony. Tony begs Dick to let him walk free, and though Dick gives no indication whether he will, Tony finds the lock on his and Lydia's cabin sprung that evening. They escape, abandoning Cuffee and Flynn, and establish a happy life together in Maryland as free people.