Defoe joined the MLS side for the 2014 campaign and has netted 11 times for the club this season, but was linked with a return to the Premier League in the transfer window.
Leiweke says that if the player doesn't want to be at Toronto they will use their designated-player tags on other targets.
He told reporters: "We will have some new DP's next year. I personally don't think Defoe will come back. I think if he doesn't want to be here, you get rid of him."
"My attitude is, if you want to be here and buy into what we've been doing, let's go roll up our sleeves and we'll fight together. And I will be with you every day. If you don't want to be here, get the hell out of our way."
Toronto are currently seventh in the MLS Eastern Conference after 26 games this season.