The Russian side are really struggling in their domestic division, but now have a serious chance of reaching the knockout stage of Europe's second-tier competition.
A first half brace from star striker Aleksandr Sobolev secured the three points for Rui Vitoria's team on a bitterly cold night in Moscow.
Napoli did pull one back through Eljif Elmas in the 64th minute of play, but the Italian outfit were unable to find an equaliser.
It was certainly a frustrating evening for the injury-depleted Serie A leaders and manager Luciano Spalletti was in no mood for niceties at full-time.
That's actually something of an understatement, because the Italian manager well and truly embodied the phrase 'sore loser' before charging down the tunnel.
Vitoria attempted to shake his opposing number's hand, but Spalletti openly refused, which prompted a quite brilliant reaction from the Spartak boss.
Check it out here...
Video: Vitoria's reaction to Spalletti's handshake refusal
Well played, Rui.
Instead of letting Spalletti's tantrum get to him, the Portuguese simply made the Napoli manager look a complete fool by standing there and looking as cool as a cucumber.
Spalletti's reaction is a clear sign that he's now really feeling the pressure after a very difficult few days.
Napoli lost their first game of the 2021/22 Serie A season at Inter Milan last Sunday, a fixture in which talisman Victor Osimhen picked up a serious facial injury that will see him miss at least three months of action.
Lorenzo Insigne is also currently injured and on top of that, the Neapolitan club are having to deal with a Covid-19 outbreak in the squad.
It doesn't get any easier for them on the weekend either, as Maurizio Sarri's Lazio are in town for a game that could prove defining to Napoli's campaign.