May, who is spending a break in Switzerland, last week appointed chancellor Philip Hammond to the role of “senior minister in charge”.
However, the position has now been rotated to the former London mayor for the second half of May's holiday. It means Johnson is effectively leading the country for the remainder of May's absence.
He is not expected to relocate from the Foreign Office to Number 10.
It comes just six weeks after Johnson pulled out of the Conservative Party leadership race, claiming he would be unable to unify factions within the party in the aftermath of June's Brexit vote.
It is also a demonstration of May's faith in Johnson after her foreign secretary endured a bruising start to his time in office.
Johnson was repeatedly confronted with previous comments on US leaders during a press conference with US secretary of state John Kerry.
May is due to return to the UK on 24 August.