The baby's parents alerted the hotel about the incident at 10 a.m. on Tuesday, and a maintenance worker was able to get the child out.
Police say the infant was reportedly in good health after being removed from the safe.
Investigators say the couple left the hotel with their baby before police arrived, but they have not returned to their home in Brooklyn, N.Y.
The hotel room was registered to a person who was driving a grey passenger van with the New Jersey licence plate B31 EUB.
There is no information about why the baby was inside the safe and police want to locate the family to find out about the welfare of the child.
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