Mbuyiseli Russel Madlanga was born and raised at the rural village of Njijini 16 kilometres outside the small town of Mount Frere, Eastern Cape Province. He is married to Nosisi Madlanga (born Nkenkana). He matriculated at Mariazell High School, Matatiele. He obtained the BJuris degree at the University of Transkei (Unitra). In 1981 – whilst doing that degree – he was awarded the Juta Prize for being the best law student. He enrolled for the LLB degree at Rhodes University. In his final year he was appointed tutor, tutoring first year law students.

After graduating, he lectured part-time in the Law Faculty of Unitra whilst working for the Department of Justice towards fulfilling his contractual obligations under a government bursary that had funded his LLB studies. He later lectured full-time at Unitra for two years. He proceeded to do an LLM in Human Rights and Constitutional Law, which he received cum laude at the University of Notre Dame in the USA. He interned at the Washington DC office of Amnesty Interntional. On his return, he did pupillage at the Johannesburg Bar.On completion, he opened practice at the Mthatha Bar.

At the age of 34 he was appointed as a Judge of the Mthatha High Court becoming South Africa's youngest judge at the time. Within only three years of this appointment, he was appointed Acting Judge of Appeal at the Supreme Court of Appeal in Bloemfontein. He was then appointed – this time on a permanent basis – as a Judge of Appeal in the Competition Appeal Court. He continued acting on the Supreme Court of Appeal Bench because the Competition Appeal Court was new and was yet to commence functioning. His acting appointment at the Supreme Court of Appeal – which was for a year – was cut short as he was then appointed to act as the Judge President of the Mthatha High Court. Whilst holding that position, he received yet another appointment; this time as an Acting Justice of the Constitutional Court of South Africa.

Personal circumstances forced him to resign from the Judiciary. He returned to the Bar as senior counsel, practising in Mthatha and Johannesburg. His practice took off immediately and he appeared in virtually all the High Courts in the country and in the Supreme Court of Appeal and Constitutional Court. Notably, he received a brief to represent the Republic of South Africa at the International Court of Justice at The Hague (Den Haag) in the Netherlands. This was in the case of the "Construction of a Separation Wall [by Israel] in the Occupied Palestinian Territory". Another brief of note that he received was his appointment by Mr Trevor Manuel, the then Minister of Finance, as the Chairperson (which – in terms of the applicable legislation – was an executive position) of the Exchange Control Amnesty Unit. This Unit did not only grant amnesty to people who had contravened Exchange Control Regulations (Regulations) in expatriating their assets, it also facilitated the disclosure of assets worth R68,6 billion, 70% of which had been taken out of the country in contravention of the Regulations. The process also raised R2,9 billion in levies. The disclosure of offshore assets resulted in an estimated R1.4 billion increase in the tax base. This is what the then Deputy Minister of Finance, Mr Jabu Moleketi, said about the Unit on completion of its task:

"I would like to take this opportunity to thank the Amnesty Unit for their sterling work. When the unit was initially announced, we did not anticipate the huge task that they would be faced with, both in the number of applications received and the associated logistics. It is through the exceptional efforts and meticulous approach of our Unit that other countries now seek to use our amnesty as an international benchmark. I wish to specifically thank the chairperson, Advocate Mbuyiseli Madlanga, who has led the Amnesty Unit impeccably and with great enthusiasm."

Yet another assignment worth particular mention was Mbuyiseli's appointment as the Chief Evidence Leader of the Marikana Commission of Enquiry. This is a Commission of Inquiry that was appointed to enquire into the killings of 34 striking mine workers and 10 other people in Marikana, near Rustenburg, North West Province in August 2012. In that capacity he was lead counsel in a team of seven advocates, three of whom (including him) were senior counsel. He held numerous other briefs in high profile cases.

On appointment by the President, Mbuyiseli became a member of the Competition Tribunal for 9 years, during 3 of which he was its Deputy Chairperson. As a nominee of the Advocates for Transformation component of the General Council of the Bar, the President next appointed him as a member of the Judicial Service Commission, a position he held for 2 years. He was then appointed – directly from his practice as an advocate – to become a Justice of the Constitutional Court of South Africa with effect from 1 August 2013, this time on a permanent basis.

At the invitation of the Law School of his alma mater, the University of Notre Dame, he held the prestigious Clynes Chair as a visiting professor. This Chair is reserved for distinguished US and international legal scholars and amongst those who have held it are US Supreme Court Justices. In that capacity he offered a two credit three week course from 4 April 2016.

Walter Sisulu University awarded him a Doctor of Laws (LLD) degree (honoris causa) at the graduation ceremony of 13 May 2016.

On 31 March 2017 Justice Madlanga was appointed as the Editor-in-Chief of the South African Judicial Education Journal, a journal scheduled for launch in April 2018 and to be published under the auspices of the South African Judicial Education Institute, a statutory body with the mandate of providing continuing education to the Judiciary.

His interests are not only in the law and academics. For 8 years Mbuyiseli was a member of the Arbitration Panel of his church, the Methodist Church of Southern Africa; having been appointed to that position by Conference, the church's highest governing body. He has also held other leadership positions which – because of space constraints – cannot be specified here.