Holyoake was born near Pahiatua in the Wairarapa region. He left formal education at age 12 to help on the family farm. Before entering politics, he was active in various local farming associations. Holyoake was first elected to Parliament in 1932, representing the conservative Reform Party. He played an instrumental role in the formation of the National Party in 1936. He lost his seat two years later but was earmarked for the safe seat of Pahiatua, which he held from 1943. Following National's first election victory, Holyoake entered Cabinet in 1949. In 1954, he was appointed the first Deputy Prime Minister of New Zealand, under Sidney Holland. Holyoake became Leader of the National Party and Prime Minister two months before the 1957 election, after Holland's resignation due to ill health. Following an election defeat, he served as the Leader of the Opposition for three years before National returned to power in 1960.
Holyoake's government rewrote the criminal legal code, passing the Crimes Act 1961. One of the main features of this act was the abolition of capital punishment, though only ten National MPs voted for its abolition. Among many conservative reforms, his government introduced a form of "voluntary unionism". In foreign policy, Holyoake supported the United States and sent troops to Vietnam. Holyoake led his party to four consecutive election victories (not since surpassed). In 1972, he resigned as Prime Minister to ease the succession for his deputy and friend, Jack Marshall.
In 1977, the National government of Robert Muldoon appointed Holyoake as Governor-General, creating controversy as opponents argued that a former politician should not hold the non-partisan position. Holyoake's term was limited to three years, not the normal five. In 1980, he became a Knight of the Garter, a rare honour.
Holyoake is to date the third longest serving New Zealand prime minister (just under 12 years), surpassed only by Richard Seddon's 13 years and William Massey's close to 13 years; he was also the first to be born in the 20th century. Holyoake was known for his diplomatic style and "plummy" voice. He was also fondly (or mockingly) known as Kiwi Keith, a name given to him in childhood to distinguish him from an Australian cousin with the same name.
Holyoake was born at Mangamutu, a short distance from Pahiatua, a town in New Zealand's Wairarapa region, the son of Henry Victor Holyoake and Esther Eves. Holyoake's great-grandparents, Richard and Eliza Holyoake, settled at Riwaka near Motueka in 1843, and his maternal great-grandparents, William and Sarah Eves, arrived in Nelson in 1842. Relatives of the 19th-century secularist George Holyoake, the Holyoakes ran a small general store at Mangamutu, and then lived for a time in both Hastings and Tauranga, before settling on the family farm at Riwaka, following the death of Holyoake's grandfather in 1913.
Holyoake was raised in the Plymouth Brethren church, and his social life as a child was very restricted. At age 12, having left school after his father's death, Holyoake worked on the family hop and tobacco farm in Riwaka. His mother had trained as a school teacher, and continued his education at home. After taking over the management of the farm, he became involved in various local farming associations, something that increased his interest in politics.