Valenti was born on September 5, 1921 in Houston, Texas, the son of Italian immigrants. During World War II, he was a first lieutenant in the United States Army Air Force. Valenti flew 51 combat missions as the pilot-commander of a B-25 medium bomber and received four decorations, including the Distinguished Flying Cross and Air Medal.

Following his death, the National Italian American Foundation (NIAF) launched the NIAF Jack Valenti Institute, which provides support to Italian American film students, in his memory. Director Martin Scorsese launched the institute at the Foundation's 32nd Anniversary Gala, after receiving an award from Mary Margaret Valenti.

Valenti graduated from the University of Houston in 1946 with a BBA. During his time there, he worked on the staff of the university newspaper, The Daily Cougar, and was President of the university's student government. Valenti would later serve on the university's board of regents.

After earning an M.B.A. from Harvard University in 1948, Valenti went to work for Humble Oil in its advertising department, where he helped the company's Texas gas stations jump from fifth to first in sales through a "cleanest restrooms" campaign.

In 1952, he and a partner named Weldon Weekley founded Weekley & Valenti, an advertising agency, with oil company, Conoco, as its first client. In 1956, Valenti met then Senate Majority Leader Lyndon B. Johnson. Weekley & Valenti branched out into political consulting and added Representative Albert Thomas, a Johnson ally, as a client. In 1960, Valenti's firm assisted in the Kennedy-Johnson presidential campaign.

In 1962, at the age of 41, Valenti married Mary Margaret Valenti. They had three children: John, Alexandra and Warner Bros. studio executive Courtenay Valenti. He died just before their forty-fifth wedding anniversary.

Valenti served as liaison with the news media during President John F. Kennedy and Vice-President Lyndon B. Johnson's November 22, 1963 visit to Dallas, Texas, and Valenti was in the presidential motorcade. Following the assassination of President Kennedy, Valenti was present in the famous photograph of Lyndon Johnson's swearing-in aboard Air Force One, and flew with the new President to Washington. He then became the first "special assistant" to Johnson's White House and lived in the White House for the first two months of Johnson's presidency. In 1964, Johnson gave Valenti the responsibility to handle relations with the Republican Congressional leadership, particularly Gerald Ford and Charles Halleck from the House of Representatives, and the Senate's Everett Dirksen.

In 1964, the FBI conducted an investigation concerning whether Valenti had a sexual relationship with a male Photographer (at a time when homosexual acts were still illegal in many states of the United States). The investigation concluded that there was no evidence that Valenti was a homosexual.

Valenti later called Johnson "the most single dominating human being that I've ever been in contact with" and "the single most intelligent man I've ever known". In a speech before the American Advertising Federation in 1965, Valenti said: "I sleep each night a little better, a little more confidently, because Lyndon Johnson is my President."

In 1966, Valenti, at the insistence of Universal Studios chief Lew Wasserman, and with Johnson's consent, resigned his White House commission and became the President of the Motion Picture Association of America. With Valenti's arrival in Hollywood, the pair were lifelong allies, and together orchestrated and controlled how Hollywood would conduct Business for the next several decades.

In 1968, Valenti created the MPAA film rating system. The system initially comprised four distinct ratings: G, M, R and X. The M rating would soon be replaced by GP, which was later changed to PG. The X rating immediately proved troublesome, since it was not trademarked and therefore was used freely by the pornography industry, with which it became most associated. Films such as Midnight Cowboy and A Clockwork Orange were assumed to be pornographic because they carried the X rating. In 1990 the NC-17 rating was introduced as a trademarked "adults only" replacement for the non-trademarked X-rating. The PG-13 rating was added in 1984 to provide a greater range of distinction for audiences.

Valenti received the Distinguished Flying Cross and Air Medal for his Service with the Army Air Force during the Second World War. In 1969, Jack Valenti received the Bronze Medallion, New York City's highest civilian honor. In 1985, Jack Valenti received the French Légion d'Honneur.

During the late 1970s and early 1980s, Valenti became notorious for his flamboyant attacks on the Sony Betamax Video Cassette Recorder (VCR), which the MPAA feared would devastate the movie industry. He famously told a congressional panel in 1982, "I say to you that the VCR is to the American film Producer and the American public as the Boston strangler is to the woman home alone." Despite Valenti's prediction, the home video market ultimately came to be the mainstay of movie studio revenues throughout the 1980s and 1990s.

Valenti later attacked film Director Oliver Stone for the 1991 movie JFK. Valenti called the movie a "monstrous charade" and said, "I owe where I am today to Lyndon Johnson. I could not live with myself if I stood by mutely and let some filmmaker soil his memory."

In 1995, he voiced a portrayal of himself on the Warner Bros. animated series Freakazoid! (close friend Steven Spielberg was the executive producer); wherein he helped recount the origin of the titular hero; he also lectured about the movie ratings by using stickers of a family; and also made frequent reference to his cheeks.

In 1998 Valenti lobbied for the controversial Digital Millennium Copyright Act, arguing that copyright infringement via the Internet would severely damage the record and movie industries.

In 2002, the University of Houston bestowed Valenti an honorary doctorate.

In December 2003, Valenti received the "Legend in Leadership Award" from the Chief Executive Leadership Institute of the Yale School of Management.

After retiring from the MPAA in 2004, Valenti became the first President of Friends of the Global Fight Against AIDS, Tuberculosis, and Malaria, an organization founded by Philanthropists Edward W. Scott and Adam Waldman. The founders wanted to support the Global Fund to Fight AIDS, Tuberculosis and Malaria in its work to prevent millions of people from dying of preventable and treatable diseases each year. Under Valenti’s leadership, Friends of the Global Fight oversaw a steady increase in U.S. funding for the Global Fund, resulting in a large-scale, positive impact in the fight against AIDS, tuberculosis and malaria. Valenti remained President of Friends of the Global Fight until his death in 2007.

In June 2005, the Washington DC headquarters of the Motion Picture Association of America, was renamed the Jack Valenti Building. It is located at 888 16th St. NW, Washington DC, very close to the White House. Jack Valenti maintained an office on the 8th floor, outside the MPAA's space, until his death.

His memoirs This Time, This Place: My Life in War, the White House and Hollywood were published on May 15, 2007, only a few weeks after his death.

In April 2008, the University of Houston renamed its School of Communication to the Jack J. Valenti School of Communication in his honor. Valenti was one of the school's notable alumni.

In the 2016 biographical film Jackie, Valenti is portrayed by actor Max Casella.