Students with disabilities who experience significant early literacy challenges need structured reading instruction. This study documents the initial efficacy of Friends on the Block (www.friendsontheblock.com), a comprehensive and flexible program designed for students with intensive early literacy needs. Elementary-age students with disabilities and intensive early literacy needs, including those with intellectual and developmental disabilities, were randomly assigned to either the Friends on the Block intervention group (n = 31) or the standard business-as-usual instruction group (n = 31). The analysis revealed statistically and educationally significant differences favoring Friends on the Block on two out of five measures of phonological awareness and all measures of decoding, word reading fluency, and comprehension. Except for one measure of listening comprehension, no differences were found on measures of language or vocabulary. Findings support increased literacy expectations for students with disabilities who require intensive literacy support, including those with intellectual and developmental disabilities.