The Netherlands international has struggled since arriving in north London for a reported fee of £18.5 million last summer, having scored just six goals in 38 appearances during his first campaign in English football.
And the deadline-day arrival of Fernando Llorente from Swansea City means Janssen would likely find himself further down the pecking order at Wembley Stadium, with Mauricio Pochettino even leaving him out of the club's squad for the group stage of the Champions League.
He reportedly rejected the chance to join Brighton late in the window while Swansea were also keen before re-signing Wilfried Bony to replace Llorente.
But Janssen is now set to ply his trade in the Super Lig, with his move set to be finalised before the transfer window closes on Friday evening.
"Our club, in principle, has agreed terms with both the player and the club to loan Tottenham and Dutch national team striker, Vincent Janssen," a statement from the Turkish club read.
"The 23-year-old striker will arrive at Istanbul Ataturk Airport at 12:30 today and negotiations will continue in Istanbul."
Janssen took to Instagram to send a message fans, both confirming the move and hoping he can regain his place at Spurs after the loan concludes.
"First of all, I would like to thank all the Tottenham Hotspur fans for their ongoing support," Janssen wrote. "I will continue in Istanbul on a season-long loan at Fenerbahce. All the best this season and see you soon! #COYS
Janssen still has three years to run on his Tottenham contract and will likely be deployed alongside compatriot Robin van Persie at his new club, while former Spurs striker Roberto Soldado has also joined the Fenerbahce ranks this summer.