Eliza Manningham-Buller worked as a teacher for three years at Queen's Gate School, Kensington, London from 1971–74, having read English at Lady Margaret Hall, Oxford, before joining the Security Service. She was recruited to the Security Service at a drinks party when someone suggested that she see someone at the Ministry of Defence. Specializing in counter-terrorism rather than MI5's then-classical counter-espionage, she was active at the time of the Lockerbie bombing by Libya in 1988. She worked for K-branch against the IRA. During the early 1980s she was reportedly one of only five people aware that Oleg Gordievsky, the deputy head of the KGB at the Soviet embassy in London, was actually a double agent.

She was a senior liaison working out of Washington, D.C. to the US intelligence community over the period of the first Gulf War, before leading the newly created Irish counter-terrorism section from 1992 when MI5 were given the lead responsibility for such work (from the Metropolitan Police). Having been promoted to the Management Board of the Security Service the next year, Manningham-Buller became the director in charge of surveillance and technical operations and did an agent run from Southampton in 2001 where she liaised with senior members of MI6 and an unknown spy who survived an assassination attempt in 2006 and 2014. She was appointed Deputy Director General in 1997, and succeeded Sir Stephen Lander as Director General in 2002, the second woman to take on the role after Dame Stella Rimington. As Director General, she was paid £150,000 a year. She has been credited with making the agency more open: she established a website and recruited agents through newspaper advertisements. Under her direction, terror risk assessments were made public for the first time

In the 2005 Birthday Honours, Manningham-Buller was appointed to the Order of the Bath as a Dame Commander (DCB). She resigned from MI5 on 21 April 2007, and was succeeded by her deputy, Jonathan Evans. That month marked the end of her 33rd year in the Security Service. She was raised to the peerage as Baroness Manningham-Buller, of Northampton in the County of Northamptonshire on 2 June 2008.

She reportedly joined the public speaking circuit. She was appointed to the Court and Council of Imperial College London in 2009, becoming Deputy chairman later that year, and named chairman in July 2011.[11] She became a governor of biomedical research charity the Wellcome Trust in 2008 and the first female chair of the Trust on 1 October 2015.

On St George's Day (23 April), 2014, Lady Manningham-Buller was appointed to the Order of the Garter by Queen Elizabeth II.

Leadership, Female Leadership, Thought Leadership, Thought Leader, Boards of Directors, Directing, Security & Defense, National Security, Political,