The new minister, Fernando Francisco Gomez Mont, is a former federal lawmaker for Calderon's conservative party who the president said would push forward justice and security reforms.
Mexico's interior minister is in charge of domestic security but also works with the country's political parties to push the government's agenda in Congress.
Calderon, speaking in a televised address, also said he had given his new minister specific instructions to work to keep organized crime out of elections.
Mexico will hold midterm elections to Congress next year. Calderon last year warned that powerful drug gangs were trying to intimidate and buy candidates.
Gomez Mont replaces Juan Camilo Mourino, who was killed last week when his small jet smashed into rush-hour traffic in Mexico City. A probe into that crash is underway.
