According to Journalducameroon.com, the gunmen stormed the Presbyterian Secondary School Nkwen before rounding off the students to an unknown destination.
A video was released on social media Monday by the apparent kidnappers, showing some of the boys saying they were taken by separatists fighting to create the independent state of Ambazonia.
The first mass abduction in Cameroon follows two major such incidents in neighbouring Nigeria, where the Islamist group Boko Haram snatched more than 200 schoolgirls from the Borno state town of Chibok in April 2014.
Armed men who stormed a Presbyterian school in Cameroon on Sunday kidnapped 78 students and absconded with the hostages to a separatist base, where a video captured one militant's chilling address to the scared group: "You will be going to school now here". "We express solidarity with the families of these children and demand that the Cameroon authorities do everything in their power to ensure all the pupils and school staff are freed unharmed".
The Principal of the school, a driver and another teacher were also kidnapped, local sources confirmed.
Militias, who have been demanding the independence of the two English-speaking regions, have called for a school boycott.
It comes after elections on October 7 in which 85-year-old Biya, who has ruled the country with an iron fist for 35 years, was credited with 71.3 percent of the vote.
Around a fifth of Cameroon's 22 million people are English-speaking - a minority whose presence dates back to the colonial period.
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The school's principal, the driver, and a teacher are still in captivity, the BBC's Mayeni Jones reports.
"We urge an immediate halt to the indiscriminate targeting of civilians and burning of houses by Cameroonian government forces and to attacks perpetrated by. anglophone separatists", State Department spokeswoman Heather Nauert said in a statement.
In the video, abductors can be seen forcing young male students to identify themselves, their parents and say they have been kidnapped by Amba Boys and they don't know where they are.
"We hope and pray they release the kids and the teachers", he added.
The Anglophone separatists maintain they are being marginalised and dominated by the Francophone majority.
A government spokesman said it was keeping track of an event but that it could not comment further.
According to United Nations figures, 246,000 people in the Southwest Region have fled their homes, and 25,000 have sought shelter in neighbouring Nigeria, many of them living hand-to-mouth in the forests.