Witty joined Glaxo UK in 1985 as a management trainee.[4] He held various positions in the UK, including director of pharmacy and distribution in Glaxo Pharmaceuticals UK.[5]
He was a vice president and general manager of marketing of Glaxo Wellcome Inc., a subsidiary of GlaxoSmithKline with responsibility for strategy development, marketing execution and new product positioning. He was an economic adviser to the governor of Guangzhou, China, from 2000 to 2002.[6]
He was appointed president, Pharmaceuticals Europe of GlaxoSmithKline plc in January 2003[6] and succeeded Jean-Pierre Garnier as CEO following his retirement in May 2008. He was paid an annual salary of £948,000 and received bonuses and other compensation amounting to £2,180,000 for this role.[7][8]
In February 2009, he pledged to make a major change in the way GSK pharmaceuticals are priced, in an attempt to make vital drugs more affordable in countries with the lowest incomes. At the same time he announced that GSK would place certain patents in a pool so that they were freely available for others in the search for new drugs.[9]
In October 2012 it was announced that he had been appointed the chancellor of the University of Nottingham with effect from 1 January 2013, having maintained strong ties with the university since graduation.[11] Witty announced his retirement from the role of chancellor in November 2017.[12]
In July 2013, the People's Republic of China announced that they were investigating allegations of fraud perpetrated by GSK going back to 2007 and involving billions of Chinese renminbi.[13] Witty stated "It appears that certain senior executives in the China business have acted outside our processes and controls to both defraud the company and the Chinese health care system. To see these allegations about people working for GSK is shameful. For me personally they are deeply disappointing."[14]
In November 2015, Witty's leadership of GSK was criticised by Neil Woodford, who said that "he’s not doing a very good job". Woodford called for GSK to be split into four companies.[18] In March 2016, Witty announced that he was to step down as chief executive.[19]
In July 2018, Witty became CEO of Optum, a division of UnitedHealth Group.[22] In November 2019, he was named president of UnitedHealth, in addition to his role as CEO of Optum.[23]
From April 2020 to December 2020, Witty took a leave of absence from Optum to assist the World Health Organization in developing a vaccine for COVID-19.[24][25] In May 2020, he was appointed to the expert advisory group for the UK Government's Vaccine Task Force, chaired by Patrick Vallance.[26]
Witty became CEO of UnitedHealth Group in February 2021.[27]
In April 2021, he was also appointed to the Pandemic Preparedness Partnership (PPP), an expert group chaired by Vallance to advise the G7 presidency held by the government of Prime Minister Boris Johnson.[28]
In 2023, Witty's total compensation from UnitedHealth Group was $23.5 million, representing a CEO-to-median worker pay ratio of 352-to-1.[29]
On 15 May 2024, a class action lawsuit was brought by the City of Hollywood Firefighters' Pension Fund alleging that Witty and two other UnitedHealth Group executives were involved in insider trading in 2023. The suit alleges that in addition to Witty, Brian Thompson and Stephen Hemsley sold a combined total of $120 million of UHC stock four months before shareholders and the general public were informed that the company was being investigated by the United States Department of Justice in regard to an antitrust suit involving Optum's potential buyout of Change Healthcare.[30]
On 6 December 2024, after the murder of former CEO of UnitedHealth Group's subsidiary company UnitedHealthcare, Brian Thompson,[31] a video was leaked in which Witty stated, "Our role is a critical role, and we make sure that care is safe, appropriate, and is delivered when people need it" and that the insurer will continue to prevent "unnecessary care" and advised that people refrain from discussing anything with the media. Some online comments made death threats in response,[32] with Fortune pointing out that UnitedHealthcare reported twice the industry average for denied claims and that "their policies contribute to medical bankruptcies and lives lost due to denied care, highlighting widespread anger at systemic issues in U.S. health care".[33]