Defoe's future has been in doubt since Toronto manager Ryan Nelsen was fired Aug. 31 and the MLS team revealed it had turned down a club record bid for the 31-year-old forward.
There has been rampant speculation that Defoe, currently nursing a groin injury back in England, wants to return to his homeland.
"I personally don't think Defoe will come back. I think if he doesn't want to be here, you get rid of him," Leiweke, president and CEO of Maple Leaf Sports & Entertainment, told Ryerson students at the Ted Rogers School of Management on Thursday.
"My attitude if you want to be here and you want to buy into what we're doing, let's go," he added. "Roll up your sleeves and we'll fight together. And I will be there with you every day.
"If you don't want to be here, get the hell out of our way."
Leiweke made his comment about Defoe not coming back after saying he expected some new designated players next year.
The club's three DPs this season are Defoe, American midfielder Michael Bradley and Brazilian forward Gilberto.
Leiweke's TFC comments, in a question-and-answer session with the students, soon found their way to English media outlets, featured on both the Daily Mirror and BBC websites.
The club had previously said that Defoe is expected back next week to continue his rehab and that he wants to be here. The former Spurs man is TFC's leading scorer with 11 goals. Toronto FC sits seventh in the Eastern Conference with a 9-11-6 record.
And while saying the team was making progress, he took a swipe at the rest of the roster while saying the fans, media and club itself were stuck in a losing tradition.
"The only two guys in our locker-room that are looking around and going we ain't going down unless we go down fighting are Michael Bradley and (new manager) Greg Vanney. We have work to do there. We're not done by any means."
"I pray that we make it to the playoffs this year," he added, "because you all deserve it. But I think we still have some hard decisions and hard work to do."
Leiweke also said he made a mistake by retaining manager Ryan Nelsen and his coaching staff for the start of the season, saying he had done it out of loyalty to Nelsen.
"Of the seven coaches we let go, not one of them had his coaching license," said Leiweke.
The MLSE boss noted that Vanney had his coaching license and taught other coaches.
In fact, former assistant coach Fran O'Leary had just finished the two-year UEFA Pro Licence course, needing only to make a final presentation, when he joined Nelsen at his introductory news conference. And a club spokesman said goalie coach Stewart Kerr also had a coaching licence.
Leiweke has announced he is leaving MLSE by June 2015 or sooner. But he continues to make headlines.