Lille had only picked up two points from their opening four games but they recorded their first win in Group B thanks to second-half goals via CSKA defender Vasili Berezutsky, who put into his own net, and Moussa Sow.
The victory on the artificial pitch at the Luzhniki Stadium lifts Lille level on five points with CSKA and Trabzonspor, who play group leaders Inter Milan later on Tuesday evening.
With playmakers Eden Hazard and Joe Cole impressing, Lille were in charge for most of the game and they could consider themselves unfortunate not to have been ahead at the interval.
The first chance fell to Cole in the 15th minute following good link-up play with Hazard. However, after creating space for himself in the area with a superb turn, he saw his low shot comfortably saved by Vladimir Gabulov.
Five minutes after that Gabulov should really have been picking the ball out of his net after Lille defender David Rozehnal won a high ball in the area and his header fell to team-mate Mathieu Debuchy seven yards out, but the France midfielder went for power over placement and his thunderous volley crashed against the crossbar and flew over.
The only time CSKA came close to a goal in the opening period was in the 28th minute when Alan Dzagoev's inswinging corner was missed by Rozehnal at the near post and Lille goalkeeper Mickael Landreau did well to keep the ball out one-handed.
Lille had another opening just before half-time when Cole's clever lofted pass was latched onto by Moussa Sow, but his close-range effort was blocked by a mixture of Gabulov and Sergei Ignashevich and from the loose ball Franck Beria fired wide.
The French champions had to resign themselves to going into half-time on level terms, but they needed just four minutes of the second period to take the lead.
Cole and Florent Balmont combined to leave Sow in a great position on the edge of the area, but the chance looked to have been wasted due to a poor first touch by the striker. However, in trying to clear the danger, CSKA defender Berezutsky inadvertently lobbed his team-mate Gabulov and the ball dropped over the line via underside of the crossbar.
That goal forced CSKA to push more men forward, but that also gave Lille chance to hit them on the break and the visitors had another good chance in the 61st minute when Cole's scooped pass put in Sow, but Gabulov did well to parry his dipping first-time shot.
Lille did not have to wait much longer to double their lead though, with Sow finding the back of the net in the 64th minute.
Hazard's superb pass picked out the run of Cole and although the on-loan Liverpool man's effort hit the inside of the post, Sow beat Gabulov to the loose ball to slide in his side's second.
CSKA briefly threatened a response when Aleksandrs Cauna's long-range shot fizzed just wide of the top corner, but Lille also had chances to increase their lead with Gabulov denying Debuchy and Hazard, and Idrissa Gana Gueye blazing over.