When she was appointed Secretary of State for International Development on 12 May 2003, following the resignation of Clare Short, Amos became the first Black, Asian and minority ethnic (BAME) woman to serve as a Cabinet minister.

In July 2010, Secretary-General of the United Nations Ban Ki-moon announced Baroness Amos's appointment to the role of Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator.

Baroness Amos, who had been serving as Foreign Office minister and as a spokesperson in the Lords for International Development was swiftly announced as Short's replacement.

[12] Her appointment made her "the UK's first black woman cabinet minister" and was an unusual example of a government department being headed by a member of the House of Lords.

On 17 February 2005, the British Government nominated Lady Amos to head the United Nations Development Programme.,[13] but the position was assigned to Kemal Derviş.

Baroness Amos left the cabinet when Gordon Brown took over as prime minister from Tony Blair in June 2007.

On 8 October 2008, it was reported that Amos was to join the Football Association's management board for England's bid to host the 2018 World Cup.

[17] In 2010, United Nations Secretary-General Ban Ki-moon announced Amos's appointment as Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator.

[20] Since 2019, Amos has been serving on the Center for Strategic & International Studies’ (CSIS) Task Force on Humanitarian Access, co-chaired by Cory Booker and Todd Young.

[23] Amos was awarded an honorary professorship at Thames Valley University in 1995 in recognition of her work on equality and social justice.

[30][31] In 2017, Amos was awarded an honorary degree at Middlesex University, thereby "recognising achievement at the highest level as well as dedication to public duty and making a difference to others' lives.

[46][47] After resigning from the cabinet, Baroness Amos took up a directorship with Travant Capital, a Nigerian private equity fund launched in 2007.