The Borussia Dortmund midfielder lasted just a minute of his side's 2-2 draw with Augsburg on Saturday before being carried off in agony.
A scan on Sunday morning confirmed that he had torn the anterior cruciate ligament in his right knee.
As a result, his season is over. The Pole has vowed to bounce back, however.
"Nothing can knock me down so quickly," he said on his club's website. "I will do all I can to come back stronger than ever."
Blaszczykowski, 28, will undergo surgery on Monday and is not expected to return until pre-season training for the 2014/15 campaign.
The Poland international has played 233 times for Dortmund since joining them from Wisla Krakow in 2007. He has scored 32 goals for Jurgen Klopp's men, who have been beset by injuries all season.
Klopp lost his entire back line in the first half of the season when Neven Subotic, Mats Hummels, Lukasz Piszczek and Marcel Schmelzer were all sidelined at the same time, forcing them to give the unattached Manuel Friedrich a contract until the end of the season.