Tomiyasu had to be replaced early in Arsenal’s Europa League exit to Portuguese club Sporting Lisbon last Thursday.
The Gunners confirmed the injury blow, with the Japanese right-back having surgery.
“Following his substitution during last Thursday’s Europa League match, subsequent assessments have confirmed that Takehiro Tomiyasu sustained a significant injury to his right knee,” Arsenal said in a statement.
“Tomi has had successful surgery in London on Tuesday and will be ruled out for the remainder of this season.”
Key centre-back William Saliba also went off injured early in the same game with a back problem, although the extent of the issue hasn’t been confirmed.
Tomiyasu’s absence will leave a hole at right-back for Arsenal if Saliba is unfit, with Ben White potentially filling in for the Frenchman.
Arsenal hold an eight-point lead atop the Premier League standings from second-placed Manchester City with 10 games to play. City have a game in hand.
The Gunners haven’t won the Premier League title since 2003-04 but are 13-time English champions.