After leaving the United Gold Coast Convention, Kwame Nkrumah founded the Convention People's Party in 1949. Kojo Botsio rose to prominence as a co-founder and leader within the party. Dr. Botsio was arrested with other prominent leaders January 17, 1950 after calling for "Positive Action" and immediate self-government. While imprisoned, Botsio was still very politically involved, even serving as a sub-committee chairman. After his release, he won a seat as the representative for the Gomoa Constituency and became the Gold Coast's first Minister of Education and Social Welfare in 1951. He later became Ghana's Foreign Minister in 1963 during the Nkrumah regime. Botsio lost his post and position in the government following Nkrumah's overthrow and the fall of Ghana's First Republic in 1966. Botsio went into exile for six years.
In 1972, after three years in power, Dr. Kofi Abrefa Busia's government was overthrown in a bloodless coup while he was receiving treatment for an illness in the UK. There was great unrest in the country following an unpopular decision by Busia to devalue the cedi by 44% in 1971. This was done in an effort to keep imports within the country's spending capacity. Colonel Ignatius Kutu Acheampong formed the National Redemption Council (NRC) and took control of the country, forcing Busia into exile. The NRC abolished the Supreme Court in 1972. The following year, on August 31, 1973, Dr. Botsio was extra-judiciously charged with plotting to overthrow the government and sentenced to death. This sentence was commuted to life and he was later released in 1977. After his release, Dr. Botsio remained active in Ghanaian politics as a leading member of the Nkrumaist People's National Party (PNP), which won the 1979 election.