James Busch Orthwein was born on March 13, 1924. His father, Percy Orthwein, was an advertising executive. His mother, Clara Busch, was the granddaughter of Adolphus Busch, the German-born founder of Anheuser-Busch.
Orthwein was educated at the Choate School in Wallingford, Connecticut. He graduated from Washington University in St. Louis.
Orthwein joined his father's advertising firm in 1947. He served as the chairman and chief executive of the D’Arcy Advertising Company from 1970 to 1983. Orthwein took the advertising agency to the global stage merging with agencies in Detroit and London. In 1985, the St. Louis-based company then merged with Benton & Bowles of New York to form D'Arcy Masius Benton & Bowles.
Orthwein served on the Board of Directors of Anheuser-Busch from 1963 to 2001. In 1997, he held 1.6 million shares in Anheuser-Busch, more than any other company insider with the exception of Chairman and President August Busch III, who was Orthwein's first cousin.
Orthwein was a co-founder of Huntleigh Asset Partners, a private investment firm, in 1983. It was later renamed Precise Capital.
Orthwein purchased the New England Patriots from Victor Kiam in 1992, when the latter was facing bankruptcy and owed him millions. During his ownership Orthwein hired Bill Parcells as head coach and oversaw the drafting of first-overall draft pick quarterback Drew Bledsoe, who helped to return the moribund franchise to respectability. He planned to relocate the Patriots franchise to St. Louis, renaming the team the St. Louis Stallions. However, those plans were derailed when Boston paper magnate Robert Kraft, owner of Foxboro Stadium, refused to accept a buyout of the lease. Kraft used his ownership of the stadium to stage a hostile takeover, offering to pay $175 million for the Patriots franchise knowing that Orthwein no longer wanted the team if he could not move it to St. Louis. Orthwein accepted the bid.
For 35 years, Orthwein was Master of Foxhounds at Bridlespur Hunt Club and he was a member of the Missouri Horseman's Hall of Fame. He helped raise more than $1-million for horse show related charities.
One of Orthwein's wives was Romaine Dahlgren Pierce, who had previously married and divorced William Simpson and David Mountbatten, 3rd Marquess of Milford Haven. Orthwein's third wife was Ruth Orthwein; they divorced in the late 1990s.
Orthwein died of cancer at his home in Huntleigh, Missouri.