An intelligence official in the area said Taliban attacked the government-run school overnight when no one was at the property.
"The girls' middle school was badly damaged because of the explosion, now the school building is almost out of use. The classrooms, desks and chairs were also damaged," Farooq Khan, a local administrative official told AFP.
The incident took place at Yousaf Kely village near Bara town, around 20 kilometres (13 miles) south of Peshawar, the capital of North West Frontier Province which has been hit by five suicide attacks in the last eight days.
Islamist militants have destroyed hundreds of schools, mostly for girls, in the northwest of the country in recent years.
Nearly 200 schools were destroyed in the Swat valley alone during a two-year Taliban uprising to enforce sharia law in a district once favoured by Western tourists for its ski slopes and mountain air.
Following up a similar offensive in Swat this summer, Pakistan has been fighting against homegrown militants in Khyber and pressing a major assault designed to crush Taliban sanctuaries in South Waziristan.
Authorities last month shut schools across Pakistan following a suicide attack on a university campus in Islamabad, although most have since reopened.