Fernando Morientes threw Monaco a Champions League lifeline by scoring a second-half away goal in Moscow.
Marat Izmailov had set Lokomotiv on their way with a brilliant opener that saw him dance past two Monaco defenders before unleashing a thunderous strike.
Vladimir Maminov added a second after the break when he drilled a low shot past Monaco goalkeeper Flavio Roma.
But Spanish striker Morientes snuck in at the far post to head home Jerome Rothen's cross to reduce the deficit.
Despite Lokomotiv not having played any competitive football for three months due to their domestic season ending in November, they were the quicker of the two teams to settle.
The Russians passed the ball around quickly and coped with the snowy conditions far better than their French counterparts.
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KEY MOMENTS
32 mins: Izmailov fires Lokomotiv into the lead
59 mins: Maminov scores a second for Lokomotiv
69 mins: Morientes reduces the deficit with a header for Monaco
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And but for the profligacy of Mikheil Ashvieta, Lokomotiv would have gone into half time further ahead than just the 1-0 lead they had acquired courtesy of Izmailov.
Monaco failed to clear the ball out of defence and Izmailov was first to it, jinking past two defenders before steadying himself to unleash a venomous strike high into the net.
Izmailov's team-mate Ashvieta had earlier wasted two gilt-edged chances to open Lokomotiv's account, the first of which saw him sky the ball over the crossbar when it looked easier to score.
Monaco gradually imposed themselves on the game as the first half progressed and were given some hope by the poor handling of Lokomotiv goalkeeper Sergei Ovchinnikov.
However, the busy Sergei Gurenko made it difficult for the visitors in midfield and he was at the heart of Lokomotiv's best moves.
After the interval, the home side sought to extend their advantage and their endeavour was soon rewarded when yet more bad Monaco defending allowed Maminov to score Lokomotiv's second.
Moments earlier, Vadim Yevseyev had gone close but Monaco goalkeeper Roma pulled off a great save.
However, his good work was undone when Monaco failed to clear the resulting corner and, after a couple of ricochets, the ball fell kindly to Maminov inside the area for him to bury his shot low to the right of Roma.
Just as the game appeared to be slipping away from Monaco, the French side won a free-kick on the left of the Lokomotiv area on 68 minutes.
Rothen floated in a lovely cross from the left that evaded the Lokomotiv defence and the onrushing Morientes timed his run to perfection to guide home a well-taken header.
Rothen then tried a cheeky free-kick on the left that had Ovchinnikov backpeddling to tip the ball over the bar as Monaco upped the tempo in search of the equaliser.
Lokomotiv may come to rue their missed chances, especially a glorious opportunity that James Obiorah fired wide at the death.
And the warmer climes of the Cote d'Azur will make Monaco slight favourites to make it to the quarter-final stage.
Lokomotiv Moscow: Sergei I. Ovchinnikov, Pashinin, Evseev,
Sennikov, Gurenko, Izmailov (Parks 79), Maminov, Loskov,
Khokhlov (Nizhegorodov 83), Asatiani, Ashvetia (Obiorah 46).
Subs Not Used: Khapov, Cesnauskis, Bilyaletdinov, Wagner.
Booked: Parks.
Monaco: Roma, Ibarra, Evra, Rodriguez, Givet, Bernardi, Cisse,
Zikos, Rothen, Prso (Adebayor 64), Morientes.
Subs Not Used: Sylva, El Fakiri, Plasil, Giuly, Hislen,
Ablancourt.
Attendance: 28,000.
Referee: Manuel Enrique Mejuto Gonzalez (Spain).