The office said in a statement Thursday that the resignation of Jose Cuitlahuac Salinas was for "strictly personal reasons." It praised his work and said he would be replaced by anti-kidnapping prosecutor Rodrigo Archundia, who would serve as acting head of the organized crime unit.
The resignation comes roughly two weeks before incoming President Enrique Pena Nieto takes office Dec. 1. Traditionally, the incoming president names a new team of federal prosecutors.
Salinas headed the Assistant Prosecutors' Office on Organized Crime since November 2011.
At least one former head of that office has been arrested on charges of helping a drug cartel. Former prosecutor Noe Ramirez has been imprisoned while on trial since 2008.