Karl Genrikhovich Vaino was born in 1923 and raised in the city of Tomsk, Siberia, in then Soviet Russia. His father Heinrich Vaino (later russified as Genrikh; 1889–1965) was an active Estonian Bolshevik who had moved to Siberia in 1918 after the Bolshevik Russian invasion into Estonia had failed in the 1918–1920 Estonian War of Independence. His mother, Liidia née Savi, was a daughter of Estonian immigrants who had settled in Siberia at the beginning of the 20th-century. After graduating from what is now the Omsk State Transport University in 1947, Vaino moved to then Soviet-occupied Estonia, and started working in engineering and technical jobs on the railway. He joined the Communist Party of the Soviet Union (CPSU) in 1947. He served as Secretary of the Communist Party's Tallinn Regional Committee from 1948–1953. In the 1960s and 1970s, he also served as Secretary of the Central Committee of the Communist Party of the Estonian SSR. He graduated from the Correspondence Higher Party School in 1957.

Having lived his early life in Russia, Vaino was a native speaker of Russian language. He was not able to speak Estonian very well, and did so with a thick Russian accent. For this, he was considered to be perfect for the role of First Secretary, being a so-called "Yestonian". On 26 July 1978, the incumbent First Secretary of the past 28 years, Johannes Käbin, who was considered to be too moderate for the ongoing Era of Stagnation Russification, was forced to resign from his post and was replaced by Vaino.

As the First secretary, Vaino acquired a reputation of being an extreme Russificator. With a dismissive attitude towards Estonian language and culture, he was not popular amongst Estonians. He delivered public speeches mostly in Russian, one notable exception being at the 350th anniversary of Tartu State University, where he presented awards to university workers, speaking in Estonian with a thick Russian accent. In 1979, an unsuccessful attempt was made on his life.^[4][5]

In early 1988, the CPE split into national communists and internationalists. Vaino was the leader of the latter, while the former was led by the Soviet ambassador to Nicaragua Vaino Väljas. Being considered too conservative by the Moscow elite, after almost 10 years, Vaino was forced to resign from his post on 16 June 1988, and replaced by Väljas. Vaino would then move to Moscow, where he had lived ever since. He did not visit Estonia again.^[6]

His daughter Eleonora Kochetova^[7] is the daughter in law of Soviet writer Vsevolod Kochetov, and his son Eduard is the Vice President for External Relations at AvtoVAZ. He has two grandsons, Russian politician Anton Vaino^[8] and Russian Interior Ministry official Andrey Vaino.

On 19 February 2022, it was announced that Vaino had died on 12 February, at the age of 98. He was buried on 14 February in the Federal Military Memorial Cemetery.^[9][10]

• 2 Orders of Lenin (1981 and 1983)
• Order of the October Revolution (1971)
• 3 Orders of the Red Banner of Labour (1959, 1965, and 1973)
• Medal "For Labour Valour" (1950)