Heston campaigned for Presidential candidate Adlai Stevenson in 1956 and John F. Kennedy in 1960. When an Oklahoma movie theater premiering his movie was segregated, he joined a picket line outside in 1961. During the civil rights march held in Washington, D.C. in 1963, he accompanied Martin Luther King Jr. In later speeches, Heston said he helped the civil rights cause "long before Hollywood found it fashionable."

In 1968, following the assassination of Senator Robert F. Kennedy, Heston appeared on The Joey Bishop Show and, along with fellow actors Gregory Peck, Kirk Douglas and James Stewart, called for public support for President Johnson's Gun Control Act of 1968. He also opposed the Vietnam War and voted for Richard Nixon in 1972.

Regarding gay rights, Heston was always supportive. "Many homosexuals are hugely talented artists and executives... also dear friends. I don't despise their lifestyle, though I don't share it," Heston stated. "As long as gay and lesbian Americans are as productive, law-abiding and private as the rest of us, I think America owes them absolute tolerance. It's the right thing to do."