Nxasana holds BCom, BCompt (Hons) degrees and a CA (SA) qualification.  He started his career at Unilever. In 1989, he established Sizwe & Co, the first black-owned audit practice in KwaZulu Natal. In 1996, he became the founding partner of Nkonki Sizwe Ntsaluba now called SizweNtsalubaGobodo which is the fifth largest audit firm in South Africa. In 1998, he joined Telkom SA as Chief Executive Officer (CEO) and was responsible for its listing on the JSE and New York Stock exchanges. Nxasana was the CEO of FirstRand Banking Group since 2005 until he retired in September 2015. Nxasana serves as chairman on various foundations and trusts. He is the co-founder and chairman of the National Education Collaboration Trust. He was appointed chairman of the National Student Financial Aid Scheme in August 2015 and chairman of the Ministerial Task Team developing a new funding model for students who come from poor and “missing middle” backgrounds.

Nxasana is now a social entrepreneur who recently founded Future Nation Schools which is a chain of affordable private schools in South Africa. He also founded Sifiso Learning Group which is involved in Edtech, academic publishing and real estate.

Nxasana has been conferred with honorary doctorates by the Universities of Fort Hare, the Durban University of Technology, the University of Johannesburg and the Walter Sisulu University.