Gaines was born in Jacksonville, Florida in 1942, the son of Charles Latham Gaines and Margaret (Shook) Gaines. At the age of ten, he and his family moved to Birmingham, Alabama. As a teenager, Gaines took up bodybuilding. He briefly attended Washington and Lee University but left school to travel around the country. He later received his BA from Birmingham-Southern College and his MFA in writing from the University of Iowa. In 1970, he moved to New Hampshire, where he taught creative writing at New England College.

In 1972, Gaines published his first novel, Stay Hungry. This work of fiction focused on the subculture of bodybuilding during the early 1970s, and revolved around the lives of three characters in Birmingham, Alabama: Craig Blake, a young heir from a family of Southern gentry; Mary Tate Farnsworth, a young woman of working-class background; and Joe Santo, a bodybuilder, athlete and Renaissance man figure of French Canadian and Menominee Indian ancestry. As well as exploring the culture of bodybuilding in great detail, the novel also dealt with themes of class difference, spirituality and self-identity. In 1976, Stay Hungry was made into a motion picture starring Jeff Bridges, Sally Field and Arnold Schwarzenegger (the latter in one of his earliest roles.)

In 1974 Gaines created Pumping Iron: The Art and Sport of Bodybuilding, a photo-essay with photographs by George Butler which focused in even further detail on the professional bodybuilding scene during the 1970s. It featured such bodybuilding greats as Arnold Schwarzenegger, Franco Columbu, Serge Nubret, Ken Waller, Mike Katz and Ed Corney, and provided a factual and philosophical exposition of the sport of bodybuilding. It is considered to be a seminal work in that field, and still enjoys significant popularity.

Pumping Iron was adapted into a documentary film of the same name in 1977, this time focusing on the 1975 Mr. Olympia bodybuilding contest and the rivalry between Schwarzenegger and up-and-comer Lou Ferrigno, though also including all of the bodybuilders from the original book. The film enjoyed great success, bringing both Ferrigno and Schwarzenegger into the spotlight and increasing their public profiles tremendously. It also helped to further popularize bodybuilding as a sport and bring it into the mainstream.

Gaines continued writing on the topic of bodybuilding, writing a biography of Charles Atlas in 1982 and publishing an exercise manual, Staying Hard: The Only Exercise Book You Will Ever Need in 1986.

In 1995 he wrote the autobiographical novel A Family Place, which documented the building of a family cabin in Nova Scotia with the help of his wife and children. In 2001 he published The Next Valley Over: An Angler's Progress, a creative nonfiction work which detailed his fly fishing experiences all over the world. He also co-authored Leaper: The Wonderful World of Atlantic Salmon Fishing with Monte Burke.

Gaines currently teaches writing part-time at the Spalding University Master of Fine Arts program, and continues to contribute articles to outdoors publications.

In 1976, Gaines returned to New Hampshire from an African buffalo-hunting safari, and discussed with his friend Bob Gurnsey the idea of a game in which the participants would stalk each other through the woods. The concept was inspired in part by the short story The Most Dangerous Game by Richard Connell. In 1981, Gaines and eleven others played the first game of paintball, using Nel-Spot pistols which were intended for marking trees and livestock by ranchers. This initial game was a capture the flag style scenario. Later, Bob Gurnsey formed the National Survival Game company, which was the first firm to sell paintball equipment.

In 1997 Gaines published a novel entitled Survival Games which features inventors of paintball, probably based upon Gaines and Gurnsey, as the main characters.