Early in the 1964 presidential campaign, Republican Barry Goldwater appeared to be a strong contender, with strong support from the South, but he lost momentum as the campaign progressed. Johnson won in a landslide, with 61.1 percent of the popular vote, the largest share of the popular vote any candidate had collected since the largely uncontested 1820 election.

On September 7, 1964, Johnson's campaign managers broadcast the "Daisy ad", which showed a little girl picking petals from a daisy, counting up to ten. Then a baritone voice took over, counting down from ten to zero, and the visual showed the explosion of a nuclear bomb. The message was clear: electing Goldwater president could lead to nuclear war. Goldwater's campaign slogan, which appeared on bumper stickers displayed by supporters, was "In your heart, you know he's right." Opponents captured the spirit of Johnson's campaign with bumper stickers that said "In your heart, you know he might" and "In your guts, you know he's nuts."

As Vice President, Hubert Humphrey was criticized for his complete loyalty to the policies of the Johnson Administration, even as many of his liberal admirers opposed the president's policies with increasing fervor regarding the Vietnam War. It was later learned that Johnson had threatened to destroy Humphrey's chance to become President if he spoke out publicly.

President Johnson's favorite dog was a terrier mix named Yuki. His daughter, Luci, found Yuki at a gas station in Texas on Thanksgiving Day 1966. The president took Yuki with him to cabinet meetings and to the Oval Office, and they even swam together in the swimming pool. LBJ danced with Yuki at his daughter Lynda's wedding. The First Lady intervened, however, when the president wanted to include Yuki in the family wedding photos.

Johnson's cowboy hat and boots reflected his Texas roots and genuine love of the rural hill country. From 250 acres of land that he was given by an aunt in 1951, he created a 2,700-acre working ranch with 400 head of registered Hereford cattle.

At 6 feet, 4 inches, Johnson towered over most colleagues, and he used that physicality to his benefit. He became known for his aggressive coercion of powerful politicians to advance legislation. When he needed a favor from someone, he'd simply stand over them with his face inches from their own, in a move dubbed "The Johnson Treatment", making promises if need be, but also predicting doom and gloom for those who weren't on his side.

Johnson vetoed a total of 30 bills (16 regular vetoes and 40 pocket vetoes), none of which were overruled by Congress.

Johnson appointed two justices, including civil rights attorney Thurgood Marshall who became the first African-American justice on the Supreme Court.

In 1964, Congress passed the Gulf of Tonkin Resolution, which granted Johnson the power to use military force in Southeast Asia without having to ask for an official declaration of war. The number of American military personnel in Vietnam increased dramatically, from 16,000 advisors in non-combat roles in 1963 to 525,000 in 1967, many in combat roles. American casualties soared and growing unease with the war stimulated a large, angry anti-war movement based chiefly among draft-age students on university campuses.

Johnson recorded an hour-long television interview with Walter Cronkite at his ranch on January 12, 1973, in which he discussed his legacy, particularly the civil rights movement. He was still smoking heavily at the time, and told Cronkite that it was better for his heart "to smoke than to be nervous". Ten days later, at approximately 3:39 p.m. on January 22, 1973, Johnson suffered a massive heart attack in his bedroom. He managed to telephone the Secret Service agents on the ranch, saying "Send Mike immediately." The agents found him unconscious and not breathing, with the telephone receiver still in his hand. Johnson was airlifted to Brooke Army Medical Center in San Antonio, where he was pronounced dead on arrival. He was 64 years old.