After spending two seasons outside Europe's premier club competition, the Turkish champion beat its Russian counterpart with high-tempo tactics and swift counterattacks in the Group D game.
Garry Rodrigues gave Galatasaray the lead in the ninth minute with a low hard shot from just outside the penalty area. Lokomotiv keeper Guilherme got a hand to the ball, but couldn't stop it.
Eren Derdiyok doubled Galatasaray's lead in the 67th when he curled a free kick around the Lokomotiv wall. Only Guilherme's outstretched hand stopped Rodrigues making it 3-0 on a breakaway in the 75th.
Galatasaray midfielder Badou Ndiaye was sent off in the 87th after earning a second yellow card for a late tackle on Anton Miranchuk.
Selçuk Inan scored Galatasaray's third from the penalty spot in stoppage time after Guilherme brought down Emre Akbaba on a counterattack.
Porto and Schalke drew 1-1 in the other game in Group D.
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