Students with special educational needs and disabilities (SEND) are at a greatly increased risk of poor academic outcomes. Understanding the factors that influence their attainment is a crucial first step towards developing more effective provision. In the current study we present a multi-level, natural variation analysis which highlights important determinants at school and individual levels in two core academic subjects (English and Maths) using a nationally representative sample of over 15,000 students with SEND attending more than 400 schools across England. We found that at the school level, inclusivity, attainment, free school meal (FSM) eligibility, behaviour (in primary schools) and linguistic diversity (secondary schools), and at the student level, age, sex, FSM eligibility, SEND provision, SEND primary need, attendance, behaviour and positive relationships each contributed to the distribution of academic attainment. Implications of these findings are discussed and study limitations are noted.