Defoe sidelined with groin strain
It means the former England international, 31, misses the MLS All-Star game against Bundesliga champions Bayern Munich on Wednesday.
In a statement on Monday, the Eastern Conference's third-placed team confirmed Defoe would miss "approximately 2-3 weeks".
Defoe's first season in the United States has been a successful one, scoring 11 league goals.
The former Tottenham forward's absence is a blow to Toronto.
Ryan Nelsen's men have key matches against the Columbus Crew and conference leaders Sporting Kansas City in the next fortnight.