The reshuffle is not expected to result in any high-profile sackings, with foreign minister and Brexit proponent Boris Johnson, pro-EU finance minister Philip Hammond and Brexit Secretary David Davis all set to keep their jobs.
But May, who heads a minority government divided over Brexit, had only limited room for change. Meanwhile, Karen Bradley became Northern Ireland secretary, while Matt Hancock took the post as the new Digital, Culture, Media and Sport minister.
Earlier, in a letter to Theresa May, James Brokenshire indicated that he is to undergo major surgery for a lesion on one of his lungs in the next few weeks.
Ostensibly, she maintains that a reshuffle was made necessary by the spate of resignations late previous year of three ministers following separate scandals, including close ally and deputy Prime Minister Damian Green, who was forced to quit over misleading statements he made regarding pornography found on his office computer.
May, who backed remain in the 2016 referendum, has had to ensure there are enough supporters of leaving the European Union in her team of ministers to satisfy rank-and-file lawmakers and ordinary members of her party that she won't deliver a watered-down version of Brexit.
The next round of talks, which will involve an effort to secure a transition period after Britain leaves the bloc and to map future trade ties, could further destabilize Mrs.
Henri Murison, the Northern Powerhouse Partnership's director, said: "It is vital that in key roles like Transport Secretary and Education Secretary, where opportunities like Northern Powerhouse Rail and improving our worst-performing secondary schools are critical, we see Secretaries of State prepared to unlock the funding and devolution of power needed to rebalance our economy for the long-term".
Former Conservative Party chairman Patrick McLoughlin, who presided over the disastrous snap election campaign, was replaced by Brandon Lewis. His role as May's chief lieutenant was filled by David Lidington, who bears the grand title of minister for the Cabinet Office and Chancellor of the Duchy of Lancaster.
The prime minister risked alienating some traditional Conservative supporters on Sunday when she abandoned a promise to overturn the ban on hunting foxes with hounds, introduced by a Labour government. May is expected to try to use the reshuffle to try to freshen the government's approach to domestic issues.
Education Secretary Justine Greening becomes the fourth minister to leave the cabinet since November past year, after resisting a request to move to the Welfare and Pensions Ministry.
But aides had long said Monday's moves were less important that those on Tuesday, when May promoted lawmakers to junior positions in preparation of a wider reshuffle after Brexit.
The government crisis was sung since forced resignation in December of its number two, Damian Green, who lied about finding in 2008 of pornographic material on his work computer.