Shamima Begum, 15, Kadiza Sultana, 16, and an unnamed 15-year-old, who are all pupils at Bethnal Green Academy, flew from Gatwick to Istanbul on Tuesday, during their half-term break.
Commander Richard Walton said he was concerned about UK girls intent on joining terror group Islamic State.
The trio are friends with a fourth girl who travelled in December.
Cdr Walton said the teenagers' families were "devastated" but there was a "good chance" the girls were still in Turkey.
He hoped a police appeal, via social media, would persuade them not to enter Syria.
They were last seen at their homes on Tuesday morning when they gave their families "plausible reasons" to be out for the day, police said.
The girls boarded a Turkish Airlines flight, which landed in Turkey on Tuesday evening.
The third girl is not being named at the request of her family.
Shamima is possibly travelling under the name of Aklima Begum, police said.
Cdr Walton said he hoped the trio would "hear our concerns for their safety and have the courage to return now, back to their families who are so worried about them."
Shamima and the unnamed 15-year-old were reported missing by their families on Tuesday evening, while Kadiza was reported missing on Wednesday morning.
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