The carrier will also fly to the destination every Saturday from Boston.
The airline will serve Owen Roberts International Airport on Mondays, Thursdays and Saturdays from New York JFK plus a Saturday service from Boston Logan.
Grand Cayman will be JetBlue’s 74th destination and its 23rd in the Caribbean.
Earlier this month, JetBlue announced intent to serve two other new Caribbean destinations in November – Cartagena, Colombia and Samana, Dominican Republic, both from JFK.
John Checketts, director of route planning for JetBlue, said: “Our Latin America and Caribbean destinations continue to flourish and based on this support that we continue to receive from our customers, we are excited to add the beautiful Cayman Islands to our growing network.”
JetBlue serves 71 cities with 800 daily flights.