Afua Nkulenu was born in the Volta Region to George Nkulenu, a blacksmith, and his wife Georgina, a potter and farmer, both of the Ewe people. Sent by her grandmother to a Presbyterian primary school, the girl advanced to a coeducational boarding school at Peki Blengo. Because of poverty, she traveled weekly from home to the school, taking food supplies each week which she cooked for herself to avoid expenses. When she won a scholarship to Achimota School, her aunt provided her with money to travel to the school. She studied there from 1936 to 1941, when she obtained the Cambridge School Certificate.

Nkulenu was the first person to start a formal food processing Business in the Gold Coast; she built up a Business supplying marmalade and orange juice to Achimota School and the RWAFF. After getting her Business established, she was sponsored by Achimota College to visit and study in England from 1949 to 1951. She was the first person of African ancestry to obtain a cooking diploma from the Good Housekeeping Institute in London and to take the post-graduate Food Preservation Course at Long Ashton Research Station, Department of Horticulture, Bristol University. She returned to Ghana. She had also married and started a family.

Ocloo worked at expanding her Business. She traveled to England in 1956 to develop recipes for commercial canning. To overcome prejudice in Ghana against locally produced goods, she formed a manufacturers' association and helped organise the first "Made-in-Ghana" goods exhibition in 1958. Encouraged by President Kwame Nkrumah, she was elected as the first President of what became the Federation of Ghana Industries, serving from 1959 to 1961. In 1964 Ocloo was the first Ghanaian woman to be appointed as Executive Chairman of the National Food and Nutrition Board of Ghana. In the mid-1960s she expanded her activities into the tie and dye textile Business.

From the 1970s onwards Ocloo worked at a national and international level in the economic empowerment of women. She was appointed as an adviser to the Council of Women and Development from 1976 to 1986, a member of Ghana's national Economic Advisory Committee from 1978 to 1979, and a member of the Council of State in the Third Republic of Ghana from 1979 to 1981. She was an adviser to the First World Conference on Women in Mexico in 1975.

She was one of the founders of Women's World Banking in 1976, with Michaela Walsh and Ela Bhatt. Ocloo served as its first chair of trustees. She received the 1990 African Prize for Leadership and numerous other honours for her work on behalf of economic empowerment of women and families. She was a member of Unity Worldwide Ministries.

Following that, she promoted the availability of credit to women, with small loans known as micro-credit, to stimulate their ability to found businesses. Making such loans to women was found to strengthen their ability to provide economically for their children and develop their families. Ocloo was a founding member and the first chairman of the Board of Directors of Women's World Banking from 1979 to 1985.

Ocloo died in Accra, Ghana after she developed pneumonia in February 2002. She received a state funeral in Accra, and was buried at her hometown, Peki Dzake.

Ocloo was a founding member of religious groups such as the Evangelical Presbyterian (E.P.) Church in Madina (a suburb of Accra) and the Unity Group of Practical Christianity (Ghana) associated with Unity Worldwide Ministries. She also assisted in forming a women’s group, known as Bible Class, in the E.P. Church, with the aim of studying the Bible and home management. She served on the synod committee of the E.P. Church for 12 years.