But her most senior colleagues - including Chancellor Philip Hammond, Foreign Secretary Boris Johnson, Home Secretary Amber Rudd and Brexit Secretary David Davis - will remain in post.
May has said she intends to stay in office "as long as people want me to serve", but past year saw numerous reports of plots to oust her - and many ministers will have their eye on a future leadership challenge.
Meanwhile, Karen Bradley became Northern Ireland secretary, while Matt Hancock took the post as the new Digital, Culture, Media and Sport minister.
When she finally emerged, it was to confirmation that she had quit the government after refusing May's suggested move to the Department for Work and Pensions (DWP).
Grayling is a close ally of the Prime Minister, having been the campaign manager for May during her successful campaign to become the leader of the Conservative party. And it couldn't have been more different from the brutal reshuffle of July 2016 that saw her dispatch heavyweights including George Osborne and Nicky Morgan to the backbenches.
It has also been reported that Justine Greening, the education minister, and Business Secretary Greg Clark could be moved to other positions in the cabinet.
- Sajid Javid was given an expanded role, adding housing to his brief in the newly-named position of housing, communities and local government minister. Mark Garnier, who was cleared before Christmas over alleged inappropriate behaviour towards his personal assistant, lost his job as a trade minister.
"They should be demoting this health secretary", he said in a TV interview criticising Hunt's performance.
Foreign Secretary Boris Johnson, a leading Brexit supporter, is expected to keep his job despite challenging May's strategy past year.
But May has said that she still hoped to lead her Tory party into the next election, which must be called by 2022.
Seven months on, there should be fewer questions about the prime minister's short-term survival, not least because few potential rivals fancy months spearheading debilitating negotiations with Brussels.
May has been forced to make changes to her top team following the resignation last month of Damian Green as first secretary of state after he admitted to lying about the alleged discovery of pornographic images on his Commons computer during a police raid.
But Monday's comings and goings were far from the radical refresh that had been trailed.
If her first long day back in Westminster is anything to go by, this year could be every bit as challenging for Theresa May as 2017.