Mlambo was appointed as an acting judge in the Labour Court and a judge in the Labour Appeal Court in 1997. He subsequently served as a judge in the South Gauteng High Court and the Supreme Court of Appeal. Prior to his appointment as High Court Judge President, he was Judge President of the Labour Court and Labour Appeal Court. During his term of office as Judge President of the Labour Court, he was critical of the practice of labour brokering which deprives employees of labour law protection. Mlambo was appointed Judge President of the Gauteng Division of the High Court by President Jacob Zuma effective from 1 November 2012, succeeding Bernard Ngoepe. He stated in his CV that he had "devoted his practice of law towards the upliftment and protection of people on the ground as a public interest lawyer and trade union lawyer". During a speech made shortly after he took office, he said he would ensure that "access to justice becomes what it should be".
An application made by eNCA, MultiChoice and Eyewitness News to the High Court in Pretoria to broadcast the proceedings of the Oscar Pistorius murder trial to be held in the court from 3 to 20 March 2014 was opposed by the defence team. On 25 February 2014, Mlambo ruled that the entire trial proceedings may be broadcast live via audio and that parts of the trial may be broadcast live via television, subject to various restrictions to minimise any impact on the trial proceedings. The parts that he permitted to be broadcast audiovisually were the opening and closing arguments, the testimony of consenting state witnesses, the judgement, and the sentencing if applicable. His ruling took into account the right to freedom of expression and the defendant's right to a fair trial. His reasons for allowing live broadcasting of the trial included dispelling perceptions that the rich and famous receive preferential treatment from the justice system, enabling public access to an unedited firsthand account of the trial, and educating the public about criminal proceedings in general. The ruling was welcomed by members of the South African media, who described it as a groundbreaking decision supporting freedom of expression, freedom of the media, open justice and democracy. In a cartoon by Zapiro published in The Times on 27 February 2014, Pistorius is depicted walking a tightrope between the justice system representing the right to a fair trial and the media representing the public's right to know. In his judgement Mlambo granted ultimate discretion regarding what may be broadcast to the presiding judge in the trial, namely Thokozile Masipa. The trial was interrupted on the second day after it transpired that eNCA was showing a still photograph of a non-consenting state witness onscreen while broadcasting her audio testimony. Masipa subsequently instructed the court that no photographs of any non-consenting witnesses may be used in the media, regardless of the source of the photographs. On 10 March 2014, Masipa ruled that the forensic pathologist's post mortem evidence may not be broadcast live, including verbatim tweeting and blogging, but reversed her ban on live tweeting and blogging the following day. A state witness was harassed telephonically after his cellphone number was read out in court during cross-examination by the defence team on the second day of the trial. In his Business Day column published on 13 March 2014, Caxton Professor of Journalism at Wits UniversityAnton Harber stated that the trial represents a turning point for local newspapers unable to compete with "the speed and conversational nature of electronic media". He also notes that the fact that the presiding judge has "her finger on the off button for live broadcast" is restraining the behaviour of the media.