Born and raised in New Orleans, Louisiana, Cambias became interested in space and astronomy at a young age. He received a degree in the History, Philosophy, and Social Studies of Science and Medicine from the University of Chicago, focusing particularly on Robert Hooke and the Royal Society. He currently lives in Western Massachusetts with his wife and two children.
His early writing focused on role-playing games, particularly adventures and support material for Space 1889. His first role playing book was published by Iron Crown Enterprises in 1994, and he has written or contributed to books for Last Unicorn Games, Hero Games, and Steve Jackson Games, including Star Trek: The Next Generation Role-playing Game, GURPS Mars, Star Hero, and GURPS Space. He is one of the founders of Zygote Games, and the co-designer of the game Bone Wars: The Game of Ruthless Paleontology, based on the Bone Wars of the late 19th century, and Parasites Unleashed, a game for younger players based on parasitology.
His first professionally published fiction appeared in 2000. This first story, "A Diagram of Rapture," was well-received and garnered nominations for the 2000 Tiptree Award and the 2001 Locus Award, as well as earning Cambias a nomination for the 2001 John W. Campbell Award for Best New Writer. He continued to primarily write short fiction for the next ten years, and his work was subsequently published in The Magazine of Fantasy and Science Fiction, The Journal of Pulse-Pounding Narratives, Crossroads: Tales of the Southern Literary Fantastic, All-Star Zeppelin Adventure Stories, Hellboy: Odder Jobs, Lady Churchill's Rosebud Wristlet, and several Year's Best anthologies.
His first full-length novel, A Darkling Sea (2014) concerns the encounter between humans and two species of sentient extraterrestrials. The book received positive reviews, mentioning the meticulous world-building and believable aliens as particular strengths. Cambias has cited his hatred of the "famous Star Trek Prime Directive" as direct influence on the book, stating that "It’s a rule which can only be invented by people who don’t need it." A Darkling Sea was nominated for the Locus Award, the John W. Campbell Memorial Award, and the Compton Crook Award, as well as the Kurd Lasswitz Prize for the German translation of the novel as "Bestes aüslandisches Werk."
His second novel is the 2015 techno-thriller Corsair, about space pirates in a near-future hard science-fiction setting. His most recent novel is titled Arkad's World, " a coming-of-age story about a human boy alone on an alien planet."  Cambias has said that follow-up novels to both Corsair and A Darkling Sea are in the works.
Cambias has become known for attending conventions and readings in semi-formal wear, often sporting a bow-tie.