Co-teaching has gained considerable interest as a service delivery model for promoting the inclusion of students with special educational needs (SEN) in mainstream classrooms. This study examines whether co-teaching has an effect on the teaching experiences of 12 students with autism spectrum disorder (ASD) and 10 students with intellectual disability (ID) as compared with the experiences of the same students in non-co-taught classes. We implemented 264 structured observations in 22 classes to identify students with SEN grouping arrangements, level of engagement, interactions with teachers and peers, and the nature of the interactions. We also conducted 44 structured interviews with co-teachers to compound their perceptions with our observations. Observational results indicate that co-teaching has a strong effect on students' with SEN level of engagement and on the nature of interactions. The grouping arrangements for these students and their interactions with teachers and peers were slightly different between co-taught and non-co-taught classes. More statistically significant differences were identified between the two conditions for students with ASD than for students with ID. Also, co-teachers reported that co-teaching had a positive effect on students with SEN in all researched variables. Our study concludes that co-teaching has some positive effect on the teaching experiences of students with SEN; nevertheless, there is still scope for improving the employment of co-teaching in Greek mainstream classrooms. Implications of these findings for current practice are discussed.