The Belgian defender headed home from a corner moments before the break to settle a scrappy encounter.
The Russian champions, who were unlucky to come away with a 2-2 draw against Shakhtar two weeks ago, dominated for much of the first half but with leading scorer Alexander Kerzhakov sidelined with an ankle injury they wasted their chances.
Shakhtar keeper Olexandr Rybka, outstanding in earning his side a point in the Donetsk clash, again came to his team's rescue, denying the home side on several occasions.
Midway through the opening half he made a double save, first stopping Igor Denisov's shot from the edge of the box before kicking away the second attempt from Konstantin Zyryanov.
Rybka also stopped a powerful header from Alexander Bukharov while winger Danny hit the post from a tight angle before Lombaerts struck with virtually the last play of the first half.
The Ukrainian champions pressed hard for an equaliser after the break but, without the injured Brazilian duo of Fernandinho and Jadson, were unable to make use of their possession.
Zenit coach Luciano Spalletti said his team were the deserved winners. "I think we played a near perfect match tonight," the Italian told reporters.
"We totally dominated the first half, taking 15 shots on goal while our opponents failed to hit the target even once. They played better in the second half but we didn't want to take too many risks and just controlled the tempo."
Zenit midfielder Roman Shirokov added: "I think you can call us the group favourites now. We still have one more home game to play against this surprising team [APOEL], but we must beat them and advance to the knockout round."
The defeat left Shakhtar, who reached the Champions League quarter-finals last season, bottom of the group on two points.
"They played better than us in the first half while we were too tight," conceded Shakhtar's Romanian coach Mircea Lucescu.
"We improved a bit in the second half, creating a few chances. But we dearly missed Fernandinho and Jadson. I think we would have looked like a different team with them playing."
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