Porto's Hector Herrera put the home side ahead in the second minute after some neat footwork from Moussa Marega. The Malian striker skipped around the Lokomotiv defence and darted to the touchline before cutting the ball back to his captain, who tapped in from close range.
Herrera then turned provider just before halftime, chipping the ball over Lokomotiv's defenders and into the path of Marega, who charged into the box and thumped his shot low between the legs of Guilherme, Russia's Brazilian-born national keeper.
Substitute Jefferson Farfan pulled one back for the Railwaymen on the hour mark, heading in powerfully from a corner, only for Jesus Corona to re-establish Porto's two-goal lead, collecting the ball in the box, cutting back onto his left foot and shooting past the outstretched Guilherme.
Porto substitute Otavio then finished the game in style, curling home a shot from the edge of the area.
The result means Porto sit top of Group D with 10 points, while Lokomotiv are out of the competition on zero points after four games. Germany's Schalke 04 are in second place on eight points, while Turkey's Galatasaray are third on four.
(Writing by Hugh Lawson in London; Editing by Toby Davis)
