The multi-role military aircraft took off from their base in Bagotville, Quebec, at 9 am local time as Canadian Defense Minister Rob Nicholson looked on.
In Romania, Nicholson said, the jets will be conducting "training activities in support of (NATO) reassurance measures" in Central and Eastern Europe to demonstrate what another official described as "the strength of Allied solidarity in response to Russian aggression."
France, Britain and Poland have already deployed fighter aircraft to Poland, Lithuania and Estonia, respectively, in response to Russia's military buildup along its border with former Soviet-era satellite Ukraine.
NATO announced this month that it would step up its defenses in Eastern Europe due to the growing crisis.
It has also deployed ships in the Baltic Sea and eastern Mediterranean.