Karen Bradley, 47, was given the job, moving from her role as head of the government's Department for Digital, Culture, Media and Sport, where she is best known for adopting a tough stance over Rupert Murdoch's bid to buy all of broadcaster Sky.
A crucial post that needed filling was the role of First Secretary of State following the recent departure of Damian Green, a close ally of May who was forced to resign just before Christmas following a breach parliamentary code.
It is being reported that Mr Brokenshire has "a small lesion on his right lung and will be having major surgery in the coming weeks".
Northern Ireland has been without a regional government for nearly a year, destabilising the delicate balance between Irish nationalists and pro-British unionists that has been shaken by Britain's June 2016 vote to leave the European Union.
During his time in the office, the MP for Hornchurch in Essex, was faced with the collapse of the Northern Irish Assembly over the Renewable Heat Incentive (RHI) scandal. He formerly served as immigration minister under former Prime Minister David Cameron.
A government source says he will be citing "ill-health", which will be confirmed in an official letter to the British Prime Minister this morning.
Ireland's Minister for Foreign Affairs Simon Coveney acknowledged Mr Brokenshire's "unfailing dedication" and his "determination" to secure political progress in Northern Ireland.
Her schedule today also includes face-to-face meetings with the leaders of the DUP and Sinn Féin.
Mr Brokenshire bore no responsibility for the breakdown between Stormont's two parties, but his response to the situation drew criticism.
In her choice of Karen Bradley as Northern Ireland secretary, Theresa May has replaced one of her former junior ministers at the home office with another.
"This is clearly a hard time for not only James but for Cathy, his wife and his children".
"We wish to express our thanks for the work Mr Brokenshire undertook in often very challenging circumstances".
"James leaves the role with a very intimate knowledge of Northern Ireland and I look forward to working with him again in the future".