The eldest of three children, Forsythe was born John (or Jacob) Lincoln Freund, on January 29, 1918, in Penns Grove, New Jersey, the son of Blanche Forsythe (née Blohm) and Samuel Jeremiah Freund, a stockbroker. Blanche was born in Georgia, to David Hyat Blohm, a Russian Jewish immigrant, and Mary S. Materson, who herself was born in Maryland, to Jewish emigrants from Prussia. Forysthe’s father was born in New York, to Polish Jewish immigrants.

He was raised in Brooklyn, New York, where his father worked as a Wall Street businessman during the Great Depression of the 1930s. He graduated from Abraham Lincoln High School in Brooklyn at the age of 16, and began attending the University of North Carolina at Chapel Hill. In 1936 at the age of 18, he took a job as the public address announcer for Brooklyn Dodgers games at Ebbets Field, confirming a childhood love of baseball. He was a lifelong active Democrat.

Despite showing initial reluctance, Forsythe began an acting career at the suggestion of his father. He met actress Parker Worthington McCormick (December 29, 1918 – July 22, 1980), and the couple married in 1939; they had a son, Dall (born February 14, 1941), and divorced in 1943. As a bit player for Warner Brothers, Forsythe successfully appeared in several small parts.

Also in 1943, Forsythe met Julie Warren, initially a theatre companion, but later a successful actress in her own right, landing a role on Broadway in Around the World. Warren became Forsythe’s second wife and in the early 1950s the marriage produced two daughters.

In 1947, Forsythe joined the initial class of the Actors Studio, where he met Marlon Brando and Julie Harris, among others. During this time he appeared on Broadway in Mister Roberts and The Teahouse of the August Moon. In 1955, Alfred Hitchcock cast Forsythe in the movie The Trouble with Harry, with Shirley MacLaine in her first movie appearance, for which she won a Golden Globe. In 1969, Forsythe appeared in another Hitchcock film, Topaz.

Forsythe was cast in a 1957 episode, “Decision at Wilson’s Creek,” on the CBS anthology series Dick Powell’s Zane Grey Theatre. He played Confederate Lieutenant David Marr who suddenly resigns to return to his wife, only to find that he is scorned by townspeople. Outdoor location sequences for the episode were shot on the Iverson Movie Ranch in Chatsworth, California, where a number of scenes took place in a group of oak trees that later came to be known as the Midway Oaks. One of those oak trees, a distinctive multi-trunked tree with a characteristic lean, became known as the Forsythe Oak, commemorating John Forsythe’s appearance at the fabled movie ranch, considered the most widely filmed outdoor location in movie and television history. The Forsythe Oak remains in place today; it is located on a private estate on the former Upper Iverson.

In 1957, he took a leading role in the situation comedy Bachelor Father for CBS as Bentley Gregg, a playboy lawyer who has to become a father to his niece Kelly (played by Noreen Corcoran), upon the death of her biological parents. The show was an immediate ratings hit and moved to NBC the following season and to ABC in the fall of 1961. On various episodes Forsythe worked with such up-and-coming actresses as Mary Tyler Moore, Barbara Eden, Donna Douglas, Sally Kellerman, Sue Ane Langdon, and a teenage Linda Evans. During the 1961–1962 season, Bachelor Father was cancelled because of declining ratings.

During the 1960s, Forsythe returned to acting in movies including Kitten with a Whip (1964), Madame X (1966) and In Cold Blood (1967). In 1964 he starred in See How They Run which is notable for being the first film made for television.

Forsythe became the highest-paid actor on television on a per-hour basis: while the show’s on-camera stars often worked 15-hour days five days a week, with a couple of hours just for hair and makeup, Forsythe’s lines for an entire episode would be recorded in a sound studio in a matter of minutes, after which he would have lunch in the network’s commissary and then leave for the track. During this period, Forsythe invested much money in Thoroughbred racing, a personal hobby. Gaining respect with the celebrity Thoroughbred circuit, he served on the Board of Directors at the Hollywood Park Racetrack starting in 1972, and was on the committee for more than 25 years.

Forsythe began a 13-year association with Aaron Spelling in 1976, cast in the role of mysterious unseen millionaire private investigator Charles Townsend in the crime drama Charlie’s Angels (1976–1981). The show starred Kate Jackson, Jaclyn Smith and Farrah Fawcett, making stars of all three but catapulting Fawcett to iconic status. Forsythe introduces the series’ concept during its opening credits:

Following heart problems, Forsythe underwent quadruple coronary artery bypass surgery in 1979. This was so successful that he not only returned to work on Charlie’s Angels, he also appeared in the two-time Academy Award-nominated motion picture …And Justice for All later that year as Judge Henry T. Fleming, the film’s main antagonist, a corrupt judge who despises Al Pacino’s lawyer character.

In 1981, nearing the end of Charlie’s Angels, Forsythe was selected as a last-minute replacement for George Peppard in the role of conniving patriarch Blake Carrington in Dynasty. Another Spelling production, Dynasty was ABC’s answer to the highly successful CBS series Dallas. Between 1985 and 1986, Forsythe also appeared as Blake Carrington in the short-lived spinoff series The Colbys.

The series reunited Forsythe with one-time Bachelor Father guest star Linda Evans, who would play Blake’s wife, Krystle. During the run of the series, Forsythe, Evans and co-star Joan Collins, who played Blake’s ex-wife Alexis, promoted the Dynasty line of fragrances. Dynasty came to an end in 1989, after nine seasons. Forsythe was the only actor to appear in all 220 episodes.

In 1992, after a three-year absence, Forsythe returned to series television starring in Norman Lear’s situation comedy The Powers That Be for NBC, co-starring Holland Taylor, Peter MacNicol, Valerie Mahaffey and David Hyde-Pierce.

In July 2002, Forsythe married businesswoman Nicole Carter (May 27, 1941 – May 11, 2010) at Ballard Country Church; they remained married until his death. Nicole Carter Forsythe died five weeks after her husband.

Besides spending time with his family, he enjoyed ownership of an art gallery. In 2005 actor Bartholomew John portrayed Forsythe in Dynasty: The Making of a Guilty Pleasure, a fictionalized television movie based on the creation and behind the scenes production of Dynasty.

On May 2, 2006, Forsythe appeared with Dynasty co-stars Linda Evans, Joan Collins, Pamela Sue Martin, Al Corley, Gordon Thomson and Catherine Oxenberg in Dynasty Reunion: Catfights & Caviar. The one-hour reunion special of the former ABC series aired on CBS. Forsythe appeared each year to read to children during the annual Christmas program near his home at the rural resort community of Solvang, California.

Forsythe died on April 1, 2010, from pneumonia in Santa Ynez, California. He was interred at Oak Hill Cemetery, Ballard, Santa Barbara County, California.