He attended San Mateo High School, graduating in 1942, and continued to aid in financing the school. He attended San Mateo Junior College and then the University of San Francisco. He was a member of the international fraternity Tau Kappa Epsilon.

By 1945, Griffin had earned enough money to form his own record label, Panda Records, which produced Songs by Merv Griffin, the first U.S. album ever recorded on magnetic tape. In 1947, he had a 15-minute Monday-to-Friday singing program on KFRC in San Francisco.

Griffin had an uncredited role as a radio announcer in the 1953 horror/science fiction classic The Beast from 20,000 Fathoms.

At one of his nightclub performances, Griffin was discovered by Doris Day. Day arranged for a screen test at the Warner Bros. Studios for a role in By the Light of the Silvery Moon. Griffin did not get the part, but the screen test led to supporting roles in other musical films such as So This Is Love in 1953. The film caused a minor controversy when Griffin shared an open-mouthed kiss with Kathryn Grayson. The kiss was a first in Hollywood film history since the introduction of the Production Code in 1934.

From 1958 to 1962, Griffin hosted a game show produced by Mark Goodson and Bill Todman called Play Your Hunch. The show appeared on all three networks, but primarily on NBC. He also hosted a prime time game show for ABC called Keep Talking. Additionally, he substituted for a week for the vacationing Bill Cullen on The Price Is Right, and also for Bud Collyer on To Tell the Truth. In 1963, NBC offered him the opportunity to host a new game show, Word for Word, which Griffin produced. He also produced Let’s Play Post Office for NBC in 1965; Reach for the Stars for NBC in 1967; and One in a Million for ABC in 1967.

Griffin was married to the former Julann Wright from 1958 to 1976; they remained friends after their divorce. The two had one son, Tony Griffin, born in 1959; Tony, in turn, had two children of his own. In an interview with The New York Times published on May 26, 2005, Griffin recalled a quip he frequently used when asked about his sexual orientation: “I tell everybody that I’m a quarter-sexual. I will do anything with anybody for a quarter.” He was otherwise secretive about the details of his business and personal life.

Griffin scored a coup when Tonight Show host Jack Paar accidentally emerged onto the set of Play Your Hunch during a live broadcast, and Griffin got him to stay for a spontaneous interview. After Paar left The Tonight Show, but before Johnny Carson took over (Carson was still hosting Who Do You Trust? for ABC), Griffin was one of the many guest hosts who presided over Tonight in the interim. Griffin was considered the most successful of the guest hosts, and was rewarded with his own daytime talk show on NBC in 1962. This live, 55-minute program was not successful, however, and was cancelled in 1963.

Griffin created and produced the successful television game show Jeopardy! in 1964; in an Associated Press profile released right before the show premiered, Griffin talked about the show’s origins:

The show, originally titled What’s the Question?, premiered on NBC on March 30, 1964, hosted by Art Fleming, and lasted for 11 years. Griffin wrote the 30-second piece of music heard during the show’s Final Jeopardy! Round, and which later became the iconic melody of the theme for the syndicated version of the show hosted by Alex Trebek.

In 1965, Griffin launched a syndicated talk show for Group W (Westinghouse Broadcasting) titled The Merv Griffin Show. The show aired in a variety of time slots throughout North America; many stations ran it in the daytime, others aired it in prime-time and a few broadcast it opposite Johnny Carson’s The Tonight Show. Griffin’s announcer/sidekick was the veteran British character actor Arthur Treacher, who had been his mentor. After Treacher left the show in 1970, Griffin would do the announcing himself, and walk on stage with the phrase: “And now…, here I come!” According to an obituary article on August 24, 2007 in Entertainment Weekly, The Merv Griffin Show was on the air for 21 years and won eleven Emmy Awards during its run.

CBS gave Griffin a late-night show opposite Carson in 1969, a move which proved disastrous. The network was uncomfortable with the guests Griffin wanted, who often spoke out against the Vietnam War and on other taboo topics. When political activist Abbie Hoffman was Griffin’s guest in April 1970, CBS blurred the video of Hoffman so viewers at home would not see his trademark American flag pattern shirt even though other guests had worn the same shirt in the past, uncensored. Griffin disliked the censorship imposed by CBS and complained.

Griffin was not shy about tackling controversial subjects, especially the Vietnam War. The guests on the Westinghouse show were an eclectic mix of entertainers, authors, politicians, and “personality” performers like Zsa Zsa Gabor. Griffin also booked controversial guests like George Carlin, Dick Gregory, Richard Pryor, Norman Mailer, and Bertrand Russell. Griffin received critical acclaim for booking such guests, but was also widely criticized for it. When philosopher and anti-war activist Bertrand Russell used Griffin’s show to condemn the war in Vietnam, Griffin was criticized for letting Russell have his say. Arnold Schwarzenegger, later the 38th governor of California, made his talk show debut in the United States on Griffin’s talk show in 1974 after moving from Austria.

In 1974, Griffin was inducted to the Hollywood Walk of Fame. In 1998, a Golden Palm Star on the Walk of Stars in Palm Springs was dedicated to him. In 2005, he accepted the degree Doctor of Laws (honoris causa) from the National University of Ireland, Galway, and in 2008, he was posthumously inducted into the Television Hall of Fame.

Griffin dedicated two shows to the topic of Transcendental Meditation and its founder Maharishi Mahesh Yogi, one in 1975, the other in 1977; the 1977 edition aired separate from the main series as a standalone special in some regions such as Canada. Griffin himself was an enthusiastic student of the practice.

In 1975, NBC canceled Jeopardy! after moving it twice on its daytime schedule, despite having an additional year on its network contract left to fulfill. Griffin produced the show’s successor, Wheel of Fortune, which premiered on January 6, 1975. Wheel, with Chuck Woolery as host and Susan Stafford as the hostess, had successful ratings throughout its network run. From December 1975 to January 1976, the show expanded to an hour, in response to the successful 60-minute version of The Price Is Right on CBS.

“Wheel” barely escaped cancellation in 1980, when NBC replaced three of its other game shows with a daytime talk show starring David Letterman; NBC finally cancelled it in 1989, when CBS picked it up for a year (only to return to NBC, when the daytime version was finally cancelled for good in 1991). The show became a phenomenon, when on September 19, 1983, a nighttime version hit the syndication market with Pat Sajak and Vanna White as host and hostess, respectively. Around the same time, Griffin composed the show’s best-known theme song, “Changing Keys”, which was used in several variants from then until 2000.

As for Jeopardy!, two different revivals of the show would be produced: one on NBC that ran for five months in late 1978/early 1979 with Art Fleming returning as host, and the other airing in first-run syndication beginning on September 10, 1984, starring Alex Trebek. The syndicated versions of both Jeopardy! and Wheel remain on the air today.

Upon his retirement, Griffin sold his production company, Merv Griffin Enterprises, to the then-Columbia Pictures Television, at the time a unit of The Coca-Cola Company, for US$250 million on May 6, 1986, the largest acquisition of an entertainment company owned by a single individual at that time. Following the sale, Forbes named him the richest Hollywood performer in history. He retained the title of creator of both his game shows.

An active desert resident, he was a supporter of the La Quinta Arts Festival and the owner of the Merv Griffin Givenchy Resort & Spa in Palm Springs, now The Parker. He owned a ranch near La Quinta, California where he raised thoroughbred racehorses, as well as St. Clerans Manor, a boutique hotel, set in an eighteenth-century estate once owned by director John Huston, near Craughwell, in County Galway, Ireland. In the 1980s, Griffin purchased the Paradise Island Resort and Casino in the Bahamas for US$400 million from Trump, but he later sold it for just US$125 million. Griffin sold his empire to The Coca-Cola Company for $250 million in 1986, then went on a buying spree of hotels, so that his wealth in 2003 was said to be around $1.2 billion.

Griffin ventured into real estate, purchasing the Beverly Hilton Hotel in Beverly Hills in 1987.

In 1988, Griffin purchased Resorts International and two of their hotels: one hotel in Atlantic City, New Jersey, and another hotel on Paradise Island in the Bahamas from Donald Trump and other investors. Part of the deal was that Trump would buy Resorts’ interest in the yet to be constructed Taj Mahal project for $273 million and Trump would own Resorts International Air which included three Sikorsky S-61 helicopters. In early 1988, Trump had wanted to take Resorts private but Griffin through Griffin Gaming & Entertainment offered the minority shareholders significantly more than Trump in April 1988. After Trump had paid $101,000,000 for Resorts International Inc. in 1987, Griffin purchased Resorts International Inc. from Trump for $365,000,000 and assumed the hotel-casino’s debt of $925,000,000 on November 15, 1988. After ten months of ownership, Griffin reported a first half loss of $46,600,000. Griffin had used $325,000,000 in junk bond financing at nearly 14% from Drexel Burnham Lambert’s Michael Milken but suspended interest payments in early 1989. Cash flow was about $70,000,000 short of what was needed to service the Resorts’ debt in 1989. Griffin subsequently sought bankruptcy court protection on December 23, 1989 for Resorts International Inc., his troubled hotel and casino operator.

GSN honored Griffin by airing ten-episode marathons of Wheel and Jeopardy! during the weekend of August 18–19, 2007. The Wheel marathon included two episodes with cameo appearances by Griffin: Sajak’s departure from the daytime version in 1989 and a 1992–93 episode that ended with Griffin, his band “The MervTones,” and White singing at a dinner club in Orlando, Florida. The Jeopardy! marathon consisted of a rerun of the Jeopardy! Million Dollar Masters Tournament from 2002.

In 1990, Griffin had an ambitious but unsuccessful attempt at adapting the venerable board game Monopoly into a game show of the same name. His last game show was a wild game show called Ruckus, which emanated from the Resorts International Hotel & Casino in Atlantic City, which he owned at the time. Involving slapstick stunts and a somewhat truncated version of his old Reach for the Stars, the show initially aired locally in New York, with the intent of national syndication early the following year. The Amazing Johnathan left the show after 65 episodes because of a contract dispute and the show was scrapped before it was to be nationally syndicated. A national audience did get a look at it, via reruns that aired for a time on GSN.

In 1991, Deney Terrio, the host of the Griffin-created Dance Fever, sued Griffin, alleging sexual harassment, but the suit was dismissed. The same year, Brent Plott, a longtime employee who worked as a bodyguard, horse trainer and driver, filed a $200 million palimony lawsuit, which was also dismissed. Griffin characterized both lawsuits as extortion. Griffin’s Los Angeles Times obituary repeated a 1991 statement he had made regarding Plott’s lawsuit: “This is a shameless attempt to extort money from me. This former bodyguard and horse trainer was paid $250 a week, lived in one of two apartments underneath my former house as part of his security function, and left my payroll six or seven years ago. His charges are ridiculous and untrue.”

Griffin’s prostate cancer, treated originally in 1996, returned and he was admitted to Cedars Sinai Medical Center in Los Angeles, where his condition deteriorated, leading to his death on August 12, 2007, at the age of 82.

The two powerhouses spun off numerous programs, and Griffin often would sign on as a creative consultant. The spin-offs included Wheel 2000 on CBS in 1997 and the short lived Jep! on GSN in 1998, both for children; Rock & Roll Jeopardy! on VH1 in 1998 for purveyors of pop music trivia; a teen-oriented game called Click!, which introduced Ryan Seacrest as its host, and—in association with Wink Martindale—Headline Chasers in 1985.

On May 14, 2003, Griffin was honored with the Broadcast Music, Inc. (BMI) President’s Award at its annual Film and Television Awards ceremony, for having created some of America’s best-known game show melodies.

On being wealthy, he said that “if people know you’re rich, they don’t talk with you when you walk down the street.” He kept his wealth an open secret, amassing media outlets, hotels and casinos with a net worth widely estimated at more than one billion dollars. Griffin stated he did not really know his worth because it “would keep me from sleeping at night”. Former First Lady Nancy Reagan and he exchanged birthday greetings each July 6 for their shared birthday. Griffin was also an honorary pallbearer at the funeral of President Ronald Reagan in 2004, having been friends with both of the Reagans for many years. Griffin was a longtime member of the Republican Party.

In 2007, Griffin’s production company, Merv Griffin Entertainment, began production on a new syndicated game show Merv Griffin’s Crosswords (originally titled Let’s Play Crosswords and Let’s Do Crosswords). The show taped in Los Angeles after initial reports that it would be produced at WMAQ-TV in Chicago. The show was produced in association with Program Partners and the William Morris Agency and began airing September 10, 2007. NBC-owned-and-operated stations in New York, Los Angeles, Chicago, San Francisco and Dallas carried the show, with many stations airing two episodes per day. The show lasted only one season, airing its last episode May 16, 2008; it has run in reruns on various channels since its cancellation.

Funeral services were held for Griffin on August 17, 2007, at the Church of the Good Shepherd in Beverly Hills. The well-attended service included Nancy Reagan; Arnold Schwarzenegger, who gave the eulogy along with Tony Griffin, Maria Shriver, and various actors, television stars, employees, and friends, including Pat Sajak, Vanna White, Alex Trebek, Dick Van Dyke, Jack Klugman, Dick Van Patten, Ellen DeGeneres, Portia de Rossi, Ryan Seacrest, Johnny Mathis, Catherine Oxenberg and Casper Van Dien. Pallbearers included Griffin Group vice-chairman Ron Ward, President Robert Pritchard, and Vice President Michael Eyre, as well as Tony Griffin. His 7-year-old grandson Donovan Mervyn was an honorary pallbearer as was Nancy Reagan. His 12-year-old granddaughter Farah gave a reading. A post-burial reception was held at the Beverly Hilton, a property owned by Griffin from 1987 to 2003. He was buried in Westwood Village Memorial Park Cemetery and his headstone epitaph (even though in his book Merv, written with David Bender in 2003, states it would be “Stay Tuned”) reads “I will not be right back after this message”, an epitaph Griffin announced on The Late Late Show with Craig Ferguson.