The 37-year-old forward suffered the injury during a World Cup qualifier for Poland against Lithuania on Sunday.
Lewandowski "has a muscle tear in the biceps femoris of his left thigh" said Barcelona in a statement, with Spanish media reporting he could be sidelined for between four to six weeks.
Barcelona face La Liga leaders Real Madrid in a Clasico at the Santiago Bernabeu on October 26th, while the forward is also set to miss Champions League matches against Olympiakos and Club Brugge among other games.
Goalkeeper Joan Garcia and playmaker Dani Olmo are also poised to miss out on the Clasico for Barça, but teenage winger Lamine Yamal returned to training on Monday after a groin problem.
Barca striker Ferran Torres was sent home from the Spain national team camp because of muscular discomfort but the club confirmed Monday he has not suffered an injury.
Torres has led the line for Barça on various occasions this season already, with Lewandowski often featuring as a substitute.