The Serbian first division club said on Thursday that Nikolic had been appointed to replace Ivan Tomic, who stepped down on Monday following a poor start to the new season.
Nikolic, who failed to win any honours during his first spell at Partizan from December 2013 to March 2015, was sacked by Slovenian champions Olimpija Ljubljana in April this year after a racial slur against one of his own players during a league game.
Nikolic, 37, called striker Blessing Eleke a "black idiot" after the striker's exuberant celebration of a stoppage-time equaliser meant his team had less time to find a winner.
"It hasn't been that long since I left and I am delighted to be back on a mission to wrestle the league title away from city rivals Red Star," Nikolic told a news conference on Thursday.
"This is a high-pressure environment but that's what the game is all about and I am looking forward to the challenge."
(Writing by Zoran Milosavljevic; Editing by Toby Davis)
