In 1958, McCombs and his fellow salesman, Austin Hemphill, moved to San Antonio to create Hemphill-McCombs Ford, which was the foundation for what ultimately became the Red McCombs Automotive Group. McCombs has served as chairman of the trustees at Southwestern University and chairman of the University of Texas's M. D. Anderson Cancer Center in Houston. His particular interest in M. D. Anderson was accentuated in 1986, when he visited a dying friend undergoing treatment there.

Today, he is the founder of the Red McCombs Automotive Group, a co-founder of Clear Channel Communications, Chairman of Academi (formerly Blackwater Worldwide). He is also a former owner of the San Antonio Spurs, Denver Nuggets, and the Minnesota Vikings, and the namesake of the McCombs School of Business at the University of Texas at Austin. in 2005 McCombs was named one of Forbes magazine's top 400 richest Americans. According to Forbes, McCombs has an estimated net worth of $1.55 billion.

In 2017, McCombs filed a $1 million civil suit against seven of his former executives whom he alleged took "trade secrets" from McCombs' company to begin a competing firm in Houston, F4 Resources. Defendants in the suit include William "Bill" Forney, Jr., who worked with McCombs for forty-four years, former chief financial officer Ricky Halkin, vice president of operations Larry Wyont, vice president of land Charles Forney, and the vice president of geology, Philip Forney. McCombs had established McCombs Energy in Houston in 1998 by merging his 50 percent interest in his partnership with William Forney with other assets purchased from Forney. McCombs claims that his former associates, however, lowered the proper payout that he was due from his investments. McCombs said that the former executives shattered personal relationships of some four decades.

Red McCombs died February 19, 2023