Phlox was born in 2080 on Denobula. Phlox had three wives, Vesena, Feezal and Nullim, each with three husbands, including Phlox, resulting in a total of 720 relationships, 42 of which had romantic possibilities. There were 31 children in his extended family, and he had five children of his own: three sons and two daughters.

Phlox became a physician in 2115 and a member of the Inter-Species Medical Exchange in 2149. In 2151, he joined the crew of Earth first warp five ship, Enterprise under the command of Jonathan Archer, serving as chief medical officer for its entire historic voyage.