Valenti left the company in 1952 to start his own advertising agency with Weldon Weekley, a classmate from the University of Houston. Weekley and Valenti, Inc., quickly became representatives of the powerful in the Houston business community as well as the powerful in Texas politics. Their political accounts included work on Dwight D. Eisenhower's presidential campaign in Texas in 1952, U.S. Representative Albert Thomas' run for Congress, John Connally's campaign for governor of Texas, and Lyndon Johnson's presidential campaign during the primaries of 1960.

Valenti had been named Outstanding Young Man of Houston in 1956, and later that year at a gathering of other young businessmen in Houston he met then-Senator Lyndon Baines Johnson. Valenti left that meeting greatly impressed, thinking of Johnson as a man who possessed strength and intelligence combined with humility and earnestness.

After he handled the press in Houston for President John F. Kennedy's November 1963 visit to Texas, Valenti's performance so impressed the vice president that Johnson convinced him to fly with the Kennedy/Johnson entourage to Fort Worth and then on to Dallas and Austin, where they would talk about the future. As Jack Valenti rode in the president's motorcade toward Dealey Plaza on November 22, 1963, the excitement of being recruited as a member of the vice president's staff turned to shock and bewilderment, when President Kennedy was assassinated by Lee Harvey Oswald. That night he found himself on Air Force One headed for Washington as one of the first staff members of President Lyndon Johnson.

In addition to becoming a close personal friend of the president, Valenti was his closest adviser, consultant, and assistant. He performed tasks at the White House in the areas of congressional relations, diplomatic matters, speech editing, and foreign relations. He attended cabinet and National Security Council meetings and was trusted with many confidential assignments. The press was skeptical and sometimes critical of Valenti's role in the White House, and rumor said that he was constantly at the mercy of Johnson's cruel scoldings and tempestuous moods. Stories were circulated that Johnson often humiliated Valenti in front of others, but Valenti refuted the reports and never spoke publicly of the president without the highest praise and loyalty.

Soon after he had taken over national security duties in April 1966, which were formerly performed by McGeorge Bundy and Bill Moyers, Valenti announced that he was leaving the White House to become president of the Motion Picture Association of America (MPAA). He spoke of his love for movies, but also of his attraction to the significant salary increase he would incur.

As head of the association representing film makers all over the country, Valenti's first and monumental contribution was to revamp the ratings. Long with the association's general counsel, Valenti wrote a new code in which he attempted to move the ratings policy away from a "taboo" mentality and instead created broad moral guidelines that would allow more artistic freedom. He also envisioned the new code as one that gave American film makers a competitive edge with the more liberated Europeans. Two pillars of Valenti's age-based system remain with us today—the "mature audiences only" rating and the "PG" rating, which allows parents to decide on an individual basis what is appropriate viewing for their children.

As he approached retirement, Valenti became embroiled in a heated controversy over the television program rating system initiated under the Telecommunications Act of 1996. Valenti led the development of the age-based system, which closely resembled the one developed earlier for motion pictures. The system was implemented in January, 1997, and quickly aroused criticism from parents, children's health, and media watchdog groups and from Congress. Critics overwhelmingly sought a change to a system based on program content, many suggesting a graded "S", "V", "L" labeling format to specify levels of sex, violence, and offensive language in programs. A Media Studies Center/Roper Center survey showed that 73 percent of Americans supported such a content-based system with only 15 percent support for Valenti's MPAA-style system. He initially insisted that the age-based system would not be changed regardless of the levels of opposition and threatened to take the issue into the courts should the government try to alter the system. Throughout the controversy, he staunchly maintained that "it is an enterprise in which government must not and cannot get involved in any way at any time for any reason, though some in government will be mightily tempted." By March, 1997, Valenti had retreated to a point where he told a Senate Commerce Committee panel that he would consider alternatives. Shortly thereafter, however, he defended the aged-based format, describing it as designed for real parents and easy to use and understand. He restated his earlier contention that it was the only system that could work effectively with a Vchip. He also maintained that primary responsibility for determining appropriateness of programs for children remained with parents arguing that "This rating system is not a surrogate maid."

Valenti suffered a defeat during the General Agreement on Tariffs and Trade negotiations when the French refused to relax import limits on U.S.-made films and television programs on grounds that its cultural identity was at stake. President Bill Clinton's decision not to sacrifice seven years of global negotiations for Hollywood was for Valenti a most unwelcome outcome.

After that unforgettable 1963 flight on Air Force One, Valenti never went back to Texas to live. He had married Mary Margaret Wiley, a former secretary to Johnson, in Houston on June 1, 1962, and as soon as he was able he brought her to Washington, D.C., where they made their home. They had three children, Courtenay Lynda, John Lyndon, and Alexandra Alice. Valenti's columns often appeared in newspapers around the country, and in December 1992 he made his debut as a novelist with Protect and Defend, a Washington insider's story about a vice president challenging his president in the primaries. Ironically, his editor at Doubleday, who published the novel, was Jacqueline Kennedy Onassis.