The 25-year-old is central to manager Michael O'Neill's strategy and would have been a first-choice selection had he been fit.
But he suffered an injury playing for his new club Palermo on Sunday and has not travelled to Belfast, leaving O'Neill with a selection headache.
The Irish Football Association confirmed the news in a brief statement on Tuesday morning.
It read: "Kyle Lafferty has been forced to withdraw from the Northern Ireland squad for the World Cup qualifier against Russia as a result of an injury.
"Lafferty suffered an Achilles injury playing for his club Palermo FC on Sunday. He has been assessed by his club and has not travelled to Belfast."
Lafferty is the second player to withdraw from O'Neill's squad, following back-up goalkeeper Michael McGovern.
Brentford striker Will Grigg, who scored twice against Sheffield United at the weekend, is considered the closest to a like-for-like replacement for Lafferty but he has just two caps and his only previous start came in a 6-0 friendly drubbing in Holland.
Inverness' Billy McKay, Huddersfield's Martin Paterson and Derby's Jamie Ward are also in the squad and pushing for selection but none of the three offers the same physical presence as Lafferty, meaning O'Neill may have to ponder a change in style.
Record goalscorer David Healy was not included in the original squad as he has yet to find a club following his release by Bury.
Northern Ireland are looking to end a winless sequence of 13 matches at Windsor Park, with O'Neill hoping for a first victory at the 10th time of asking.