Born in New York City, Fixx was a graduate of Oberlin College in Ohio. His father, Calvin Fixx, was an editor at TIME who worked with Whittaker Chambers.

Fixx was a member of the high-IQ club Mensa and published three collections of puzzles: Games for the Super-Intelligent, More Games for the Super-Intelligent and Solve It! The back flap of his first book says: "...He spent his time running on the roads and trails near his home, training for the Boston Marathon."

Fixx started running in 1967 at age 35. He weighed 240 pounds (110 kg) and smoked two packs of cigarettes per day. Ten years later, when his book, Complete Book of Running (which spent 11 weeks at No. 1 on the best-seller list) was published, he was 60 pounds (30 kg) lighter and smoke-free. The book inspired millions of people. In his books and on television talk shows, he extolled the benefits of physical exercise and how it considerably increased the average human being's life expectancy.

The cover of Jim Fixx' book, The Complete Book of Running, featured Fixx's muscular legs against a red cover. The book sold over a million copies.

In 1980, Fixx wrote a follow up book entitled Jim Fixx's Second Book of Running: The Companion Volume to The Complete Book of Running.

In 1982, Fixx published Jackpot!, the story of what happened after the publication of The Complete Book of Running when he experienced the "Great American Fame Machine", becoming richer and more celebrated than he could have imagined. In one account, he noted an experience of being on a TV show with George Harrison, and noticed that Harrison was not sitting down in the "green" room. Upon inquiry, Harrison said that sitting down wrinkles the pants. He had become a guru of the running boom.

Maximum Sports Performance, published posthumously, discusses the physical and psychological benefits of running and other sports, including: increasing self-esteem; acquiring a "high" from running; and being able to cope better with pressure and tension.

On 20 July 1984, Fixx died at the age of 52 of a fulminant heart attack, after his daily run, on Vermont Route 15 in Hardwick. The autopsy revealed that atherosclerosis had blocked one coronary artery 95%, a second 85%, and a third 70%.[citation needed] The death of Fixx was an ironic fact that contradicted one of the most popular myths that the running boom in the '70s spawned: that distance running conferred an invulnerability to the diseases of modern life, particularly heart disease. Some who opposed his beliefs said this was evidence that running was harmful. In 1986, exercise physiologist Kenneth Cooper published an inventory of the risk factors that might have contributed to Fixx's death . Granted access to his medical records and autopsy, and after interviewing his friends and family, Cooper concluded that Fixx was genetically predisposed (his father died of a heart attack aged 43 and Fixx himself had a congenitally enlarged heart) and several lifestyle issues (Fixx was a heavy smoker prior to beginning running aged 36, he had a stressful occupation, he had undergone a second divorce, and his weight before he took up running had ballooned to 220lbs).

A carved granite monument—a book with an inscription to Jim Fixx from the people of northeast Scotland—now stands in Hardwick Memorial Park, in Hardwick.

Many late-show hosts and stand-up comedians, including Bill Hicks and Denis Leary, did routines on Jim Fixx, notably on the irony of Fixx's abrupt death in light of being viewed as a health guru. Bill Hicks contrasted his death while running with the fact that Keith Richards is still alive and sounding good.