He was the son of Dato' Onn Jaafar, the founder of UMNO and a Malayan freedom fighter. His grandfather Dato Jaafar Haji Muhammad was the first Menteri Besar of Johore while his grandmother, Hanim Rogayah was from Scarcia, Turkey. He was the brother in law of Tun Abdul Razak, his predecessor as Prime Minister, who also married another Tan Sri Haji Mohamad Noah Omar's daughter, Tun Rahah Mohamad Noah.
Tun Hussein married Tun Suhaila Noah in 1948. Suhaila Noah was the daughter of Tan Sri Haji Mohamad Noah Omar, former Minister of Home Affairs and first Speaker of the Dewan Rakyat. Hussein Onn and Suhaila Noah had six children, including their fourth child, Hishammuddin Hussein, the Minister of Defence since 2013. Their eldest daughter, Datin Roquaiya Hanim, died on 17 September 2005, at the age of 56 from breast cancer in Kuala Lumpur.
Tun Hussein received his early education in Telok Kurau Primary School, Singapore and at the English College Johore Bahru. After leaving school, he joined the Johor Military Forces as a cadet in 1940 and was sent a year later to the Indian Military Academy in Dehradun, India. Upon completion of his training, he was absorbed into the Indian Army served in the Middle East when the Second World War broke. After the war, his vast experience prompted the British to employ him as an instructor at the Malayan Police Recruiting and Training Centre in Rawalpindi.
Tun Hussein came back to Malaysia in 1945 and was appointed Commandant of the Johor Bahru Police Depot. The following year he joined the Malaya Civil Service as an assistant administrative officer in Segamat, Johor. He was later posted to the state of Selangor, becoming Klang and Kuala Selangor's district officer.
Tun Hussein, who came from a family with deep nationalistic spirit and political roots, resigned from the civil service to go into politics. In 1949, he became the first youth chief of UMNO (United Malays National Organisation), a party his father helped established. In 1950, he was elected the UMNO secretary general. Tun Hussein however left UMNO in 1951 to join his father in forming the Independence of Malaya Party (IMP).
With IMP losing momentum, Tun Hussein went to London to study law and was called to the Bar and admitted as a member of the Honourable Society of Lincoln's Inn, qualifying as a Barrister-at-Law. He came back as a certified lawyer and practised in Kuala Lumpur.
Hussein Onn returned to politics in 1968 after being persuaded by the then Deputy Prime Minister Tun Abdul Razak to rejoin UMNO. He stood and won the general elections in 1969 and was appointed as the education minister. Tun Hussein's meteoric rise continued on 13 August 1973 when he succeeded the late Ismail bin Abdul Raman as the Deputy Prime Minister. On 15 January 1976 he was appointed as Prime Minister of Malaysia after the death of Tun Razak.
Hussein was renowned for stressing the issue of unity through policies aimed at rectifying economic imbalances between the various communities found in Malaysia. For instance, 20 April 1981 saw the National Unit Trust Scheme being launched. He also gave serious consideration to the concept of Rukun Tetangga (a neighbourhood watch scheme) and the fight against the drug menace.
He underwent a coronary bypass in early 1981. On 17 July the same year, he retired from active politics and relinquished his prime minister post due to health concerns. He was succeeded by Mahathir bin Mohamad, his deputy.
After his retirement as Prime Minister, he continued to contribute to welfare organisations. He was instrumental in the setting up of the Tun Hussein Onn Eye Hospital. He was also an advisor to Petronas, the country's oil company, and Chairman of Institute of Strategic and International Studies (ISIS).
During the 1987 UMNO leadership crisis, Hussein fell out with Prime Minister Mahathir Mohamad, supporting Team B along with Tunku Abdul Rahman. Hussein along with the Tunku, henceforth, became a strident critic of the Mahathir administration and died without having rejoined UMNO.
Hussein Onn died on 29 May 1990 in Seton Medical Center at San Francisco, California, at the age of 68. He had two sons and four daughters. He is buried in Makam Pahlawan (Heroes Mausoleum) near Masjid Negara, Kuala Lumpur. Malaysia : Grand Commander of the Order of the Defender of the Realm (1981)
Several places were named after him, including:Bandar Tun Hussein Onn, a townships in Cheras, Selangor.
Desa Tun Hussein Onn, a village near Setiawangsa, Kuala Lumpur.
Tun Hussein Onn Jamek Mosque, a mosque in Larkin, Johor, Johor.
Universiti Tun Hussein Onn (UTHM) Batu Pahat, Johor.
Institut Pendidikan Tun Hussein Onn (IPTHO) Batu Pahat, Johor.
Kolej Tun Hussein Onn (KTHO) Universiti Kebangsaan Malaysia (UKM) Bangi, Selangor.
Kolej Tun Hussein Onn (KTHO) Universiti Teknologi Malaysia (UTM) Skudai, Johor.
Sekolah Menengah Kebangsaan Tun Hussein Onn (SMKTHO), a secondary school in Kluang, Johor and Seberang Jaya, Penang.
Sekolah Kebangsaan Tun Hussein Onn (SKTHO), a primary school in Kampung Pandan, Kuala Lumpur.
Tun Hussein Onn National Eye Hospital, Petaling Jaya, Selangor.
Tun Hussein Onn Highway, part of the Penang Bridge, Penang.
Jalan Tun Hussein Onn, a major road in Putrajaya.