The School Governing Body (SGB) made the decision following a meeting with parents to address the issue at 07h30 on Wednesday morning.
This left the school's more than 1400 learners and their teachers locked outside the gates of the building in Dower Avenue.
The SGB is believed to be disgruntled due to the shortage of four Heads of Department's (HOD's) and five post-level one vacancies.
Acting Principal, William Human, said mostly grade eight and nine learners were affected.
"Certain grade eight and nine classes have been affected with no teaching in some subjects since the beginning of the academic year," he said.
Human said they need HOD's for Social Sciences, Commercial Sciences, English, and isiXhosa.
There are also post-level one vacancies for isiXhosa, Afrikaans, Technology, Natural and Social Sciences.
"All these subjects, except Xhosa, then need to be taught in both English and Afrikaans," he said.
Human said this is a long-running issue that the department has been aware of since last year.
According to the SGB they previously emailed the department to highlight their concerns and to set up a meeting with the Education District Officer (EDO) on Monday.
This meeting, however, was not honoured due to the EDO's prior commitments.
The SGB and other concerned parents marched to the town's district education office after closing the school and obtaining permission from the police to do so.
Meanwhile, several public schools in Makhanda were also shut down on Wednesday by the town's School Governing Body Forum.
The Chairperson, Nosgqibo Soxujwa, said this came due to the Education Department's failure to deliver textbooks and stationery.
She said teacher assistants and general assistants have also not yet been paid since January, while others have not received their stipends since December.
Soxujwa said the forum will convene again next Tuesday, as they await further response following a protest outside the provincial department last week.
St Mary's, Good Shepherd, and Fikizolo Primary schools as well as Ntsika and Mary Waters High School are amongst the schools affected by the shutdown.