German aircraft leaving for the Middle East include two Tornado jets and a transport plane with 40 soldiers and ground crew from Jagel airbase in Schleswig-Holstein.
"This is certainly a dangerous deployment," Wing Commander Michael Krah said on Wednesday.
But Krah added that "one can never have too much reconnaissance," insisting that the German aircraft would bring a valuable contribution to the coalition mission against Isis despite not directly bombing the enemy.
An air-to-air refuelling plane will also lift off from Wahn airbase near Cologne.
But the full complement of six German Tornados won't be flying their first missions over Syria until the new year.
MPs voted on Friday to allow 1,200 soldiers and aircraft, as well as the navy frigate Augsburg, to join the mission against Isis in Syria.