Balotelli scored twice in the opening half hour to give the hosts a two-goal cushion, and take his tally to 21 goals this season for Nice.
The maverick Italian slotted home after four minutes and converted a penalty in the 28th, sending Lokomotiv keeper Guilherme the wrong way after a Nemanja Pejcinovic handball.
But not to be outdone, Fernandes pulled one back from the spot and Nice's Racine Coly saw red for fouling Ari.
The former Portsmouth and Everton loanee scored the resulting free-kick in the 67th minute, before completing his second Europa League hat-trick this term from Anton Miranchuk's cross.
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