It was founded in 2012 by Peter Hyman, a former special adviser to Prime Minister Tony Blair.

School 21 was co-founded by Ed Fidoe, an educational consultant and ex-theatrical producer, Oli de Botton, a teacher and ex-consultant, and Peter Hyman, an ex-speechwriter and special adviser to Prime Minister Tony Blair and the former deputy head teacher of Greenford High School in Southall.

[6] Free schools are exempt from the National Curriculum for England,[14] though they must still teach a "broad and balanced" curriculum that includes Relationship and Sex Education, religious education, and the subjects of English, maths, and science.

[5][18] The school's ethos and curriculum is built around developing six attributes in its students for success in the 21st century.

[23] Oracy is central to the curriculum, and the school has developed a framework for the subject with the University of Cambridge.

[26] The school does not follow a usual schedule of periods where a single teacher teaches classes of 30 students, but instead combines lectures, classes, one-on-one coaching sessions and seminars, and there are also free periods for students in the secondary school phase.

[31][32] In the 2021/2022 academic year, students at School 21 took GCSEs in art and design, biology, chemistry, computer studies, drama and theatre studies, English language, English literature, geography, history, mathematics, music, physical education, physics, Polish, Double Award Science, and Spanish.

Students also took technical awards in hospitality, general music studies, and speech and drama.