Raiders have caused 'extensive mindless damage' at Medlar with Wesham Church of England Primary School, police said.
They broke into the Garstang Road North school between 4am and 4.35am today before going on their wrecking spree.
PC Oliver Maughan, from Fylde Police, said: "The offenders broke into the school and have caused extensive mindless damage.
"This crime has caused disruption and upset to the staff, teachers, parents and the children alike."
Headteacher Liz Astbury said she believes the burglars were after money, and said office rooms were cordoned off this morning so crime scene investigators could search for evidence.
A safe was taken out of school but was unopened and is now in the hands of police, she said, adding: "We keep minimal money on the premises. It has been mindless damage and fruitless."
Mrs Astbury said a caretaker was alerted by an alarm, while a spokesman for Lancashire Police said officers were called at around 4.30am to reports of a break-in.
"The classrooms are okay," Mrs Astbury added. "It's business as usual. All my staff knew before they came to school so they were fully prepared.
"The children are being taught as normal, and the police are investigating."
The vandals got into the school after damaging a window, the police spokesman added.
No arrests have been made, and officers have appealed for anyone with information to come forward by calling 101, quoting WA1719067.