Although the neural systems supporting single word reading are well studied, there are limited direct comparisons between typical and dyslexic readers of the neural correlates of reading fluency. Reading fluency deficits are a persistent behavioral marker of dyslexia into adulthood. The current study identified the neural correlates of fluent reading in typical and dyslexic adult readers, using sentences presented in a word-by-word format in which single words were presented sequentially at fixed rates. Sentences were presented at slow, medium, and fast rates, and participants were asked to decide whether each sentence did or did not make sense semantically. As presentation rates increased, participants became less accurate and slower at making judgments, with comprehension accuracy decreasing disproportionately for dyslexic readers. In-scanner performance on the sentence task correlated significantly with standardized clinical measures of both reading fluency and phonological awareness. Both typical readers and readers with dyslexia exhibited widespread, bilateral increases in activation that corresponded to increases in presentation rate. Typical readers exhibited significantly larger gains in activation as a function of faster presentation rates than readers with dyslexia in several areas, including left prefrontal and left superior temporal regions associated with semantic retrieval and semantic and phonological representations. Group differences were more extensive when behavioral differences between conditions were equated across groups. These findings suggest a brain basis for impaired reading fluency in dyslexia, specifically a failure of brain regions involved in semantic retrieval and semantic and phonological representations to become fully engaged for comprehension at rapid reading rates.