The former St Mirren and Queen of the South manager will be making his return to the dug-out - after 20 months out of the game - by taking charge of the Hampden club.
MacPherson has been selected from a shortlist of more than 30 candidates after a rigorous process set out by the part-time side.
The 45-year-old was in charge of St Mirren from December 2003 to May 2010 and during his time the team won the Challenge Cup as well as the First Division and promotion to the top flight.
Queen's are stuck at the bottom of SPFL League 2, some 10 points behind an Elgin City side they defeated 2-0 on Saturday under the guidance of interim coach Richard Sinclair.
MacPherson's first match in charge of the club will be a trip to face Peterhead, the league leaders, on Saturday.