An ambitious Brexiteer and free market enthusiast from the right of the party, she had been tipped for further promotion in a Cabinet in which Mrs May was keen to highlight female talent.
She is widely believed to harbour leadership ambitions, and some Westminster-watchers regard her "freelancing" meetings with members of the Israeli government as part of a possible drive to boost her personal contacts and standing ahead of an eventual pitch for the top spot.
Elected to Parliament in 2010 at the age of 38, she achieved ministerial rank just four years later as exchequer secretary to the Treasury, before promotion to employment minister following David Cameron's 2015 general election victory.
She was one of the ministers who took advantage of Mr Cameron's decision to allow members of his Government to argue on both sides of the EU referendum and played a prominent role in the Leave campaign.
Along with Boris Johnson, David Davis and Liam Fox, she was among a group of convinced Brexit-backers brought into the Cabinet by Mrs May in July last year, as the new Prime Minister sought to unite her party in the wake of the divisive referendum battle.
Her appointment as International Development Secretary was greeted with concern by some in the aid community, who recalled that she had previously called for her new ministry to be replaced by a Department for International Trade and Development with greater focus on boosting UK business opportunities in the developing world.
But she backed away from the idea, committing herself to DfID continuing in its current form and backing Britain's legal commitment to spend 0.7% of gross national income on aid.
The 45-year-old was born in Harrow, north London, the daughter of parents who came to Britain from Idi Amin's Uganda in the 1960s.
She studied at a comprehensive school in Watford before taking a degree in economics, sociology and social anthropology at Keele University and a post-graduate diploma in government and politics at Essex.
She joined the Tories as a teenager but spent two years in the Referendum Party, which campaigned for a vote on EU membership in the mid-1990s.
She was recruited to William Hague's press office during his leadership, then left politics for a career in public relations.
After unsuccessfully fighting Nottingham North in the 2005 election, she was placed on Mr Cameron's priority A-list of promising candidates and won a seat at Westminster as MP for the newly-created Witham seat in Essex.
She was one of a group of young right-wing Tories behind the 2012 book Britannia Unchained, which challenged the low productivity of British workers and suggested the UK should follow the economic model of countries like Singapore.