Neelix grew up with his parents, his sisters, and his brothers on Rinax, a moon of the Talaxian homeworld. For a number of years, the Haakonians were at war with the Talaxians. At some point, the Talaxian government called on Neelix to serve, but he went to Talax to avoid military service (and anyone refusing to serve during wartime was given a death penalty) because he felt the war was wrong. While he was on Talax in 2356, the Haakonians unleashed the metreon cascade on Rinax whereby in the blink of an eye Rinax was enveloped by a deadly cloud. The day after the cascade, Talax surrendered to the Haakonian Order.

After the death of his family and the destruction of his homeworld and what was left under alien rule, Neelix left the system to move on with his life. He served on a mining colony for a while and worked for two years as an engineer's assistant aboard a Trabalian freighter where he became well-versed in warp theory. He also spent six years aboard a Talaxian garbage scow. Eventually, Neelix would become a merchant and buy his own cargo ship, the Baxial.

At some point, Neelix met an Ocampa, named Kes while she was being held captive by the Kazon-Ogla. The two feel in love but he was unable to rescue her. Neelix discovered a debris field near the Ocampa homeworld and claimed it for himself. He was discovered there in 2371 by the crew of the Starfleet vessel Voyager, and agreed to help them find their missing crew members, who had been sent to the planet Ocampa. Once on the planet, he was finally able to rescue Kes and helped the Voyager crew find their missing people.

Both Neelix and Kes joined Voyager's crew, where Neelix acted as a guide to the Delta Quadrant, a cook and the moral Officer. A few years later, Neelix and Kes ended their relationship. He stayed with Voyager for most their travel in the Delta Quadrant, were he befriended Lieutenant Commander Tuvok, whom tolerated him. He also became Godfather to Naomi Wildman.

In 2378, Voyager discovered a group of Talaxians living inside an asteroid located in the Delta Quadrant. Neelix helped them defend themselves against a group of miners that wanted them to leave the ore-rich asteroid. It was also at this time that Captain Janeway offered him a chance to serve as Starfleet's permanent ambassador in the Delta Quadrant. He accepted the position and soon left the starship to live with the other Talaxians inside the asteroid. Neelix stayed with Dexa, a widow, and her son, Brax. However, Neelix also continued to keep in contact with the crew of Voyager.