The striker, who will join Bundesliga leaders Bayern Munich at the end of the season, has been in fine form for Dortmund so far in 2013-14, as he has scored 22 goals in 34 appearances.
Lewandowski had been due to captain Poland on Wednesday in Warsaw in the absence of Dortmund team-mate and regular skipper Jakub Blaszczykowski.
However, the former Lech Poznan forward will miss the chance to lead out Adam Nawalka's side as Poland look to build towards the UEFA Euro 2016 qualifiers.
And the 25-year-old could also miss out on Dortmund's Bundesliga meeting with Freiburg on Sunday.
"I have a slight tear of the cruciate ligament. The doctor says I shouldn't play on Sunday," Lewandowski told Bild.
Lewandowski's prospective absence will come as a blow to a Dortmund side already missing Blaszczykowski, Neven Subotic, Sven Bender and Ilkay Gundogan through long-term injuries.
A statement on Dortmund's official website read: "Borussia Dortmund striker Robert Lewandowski will not be in action for the Polish national team on Wednesday. He is unavailable for the match against Scotland because of knee problems.
"After his return from Warsaw to Dortmund Lewandowski will be examined by team doctor Markus Braun, to diagnose the precise extent of the injury."
