This is an investigation of the knowledge and awareness of Autism Spectrum Disorder among secondary school teachers in Ekiti State, Nigeria. It is a school-based cross-sectional study using a multi-stage sampling method to select local government areas, secondary schools, and participants for the study. A total of 107 teachers selected from 21 secondary schools in 2 local government areas participated in the study. A Survey of Knowledge of Autism Spectrum Disorder (ASK-ASD) was used to assess knowledge while an ordinary awareness questionnaire was used to assess the teachers' awareness of the disorder. Using Pearson correlation coefficient and one-way Analysis of Variance to test five hypotheses, results showed no significant relationship between knowledge of Autism Spectrum Disorder and participants having a family or friend with the disorder (r (105) = -.113 p>.05). Finding also revealed a significant relationship between knowledge of Autism and prior training on Autism (r(107) = -.266 p<.05). Age has a significant influence on knowledge of the disorder (F (2, 98) = 4.29 p<.05) but school type (F (2, 104) = 2.506 p>.05) and teaching experience (F (2,103) = 1.971 p>.05) do not have a significant influence on knowledge of Autism. The result further shows that 96.2% of the participants were aware of the disorder while 3.8% were unaware of it. It was recommended that secondary school teachers be equipped with information about Autism Spectrum Disorder through periodic seminars, workshops, and conferences.