[5] [6] In the December 2020 Ghanaian presidential election, Opoku-Agyemang was selected by John Mahama as his running mate on the NDC party ticket.

In March 2007, she was one of five scholars selected to deliver presentations during the 200th Anniversary of the Abolition of Slavery at the United Nations Headquarters in New York City.

[12] In October 2009, she was elected Ghana's representative to the executive board of the United Nations Educational, Scientific and Cultural Organisation (UNESCO).

As an academic, she has written and published in scholarly journals and presented articles at various conferences including at the 200th Anniversary of the Abolition of Slavery at the United Nations Headquarters in New York City[12] and at the Inaugural Lecture to the Ghana Academy of Arts and Sciences.

Her leadership drove the implementation of policies that tackled gender disparities, promoted higher female enrolment and retention rates, and empowered girls through education.

[23][24] Additionally, she led the conversion of 10 polytechnics across the regions into technical universities, a bold initiative that elevated the status of these institutions, broadening their academic scope and enhancing vocational education.

[26][27] This reform was instrumental in aligning Ghana’s educational framework with global trends, equipping students with practical skills for a competitive job market.

[28] During her tenure, Opoku-Agyemang initiated the construction of 124 Community Day Senior High Schools, known as "E-Blocks," to improve access to secondary education in underserved areas.

[29] By the end of her term, 50 schools were completed and operational, providing modern facilities such as science laboratories, libraries, and ICT centres.

[31] The university was inaugurated by President John Dramani Mahama in November 2015, underscoring the government's commitment to expanding access to quality higher education and supporting the training of health professionals to address national healthcare needs.

[33]Opoku-Agyemang was selected as the presidential running mate for the National Democratic Congress (NDC) on 6 July 2020 for Ghana’s December 2020 General elections.

[37][38][39][40] She appealed to Ghanaians to vote for change and promised to use her office as vice president to influence sustainable development and practical youth-centred policies.

[40][41][42] The NDC National Executive Committee, on 7 March 2024, officially endorsed Opoku-Agyemang again as the running mate for the party's flagbearer, ahead of the 2024 general elections.