The goal of cognitive neuroscience is to integrate cognitive models with knowledge about underlying neural machinery. This significant challenge was explored in relation to word reading, where sophisticated computational-cognitive models exist but have made limited contact with neural data. Using distortion-corrected functional MRI and dynamic causal modeling, we investigated the interactions between brain regions dedicated to orthographic, semantic, and phonological processing while participants read words aloud. We found that the lateral anterior temporal lobe exhibited increased activation when participants read words with irregular spellings. This area is implicated in semantic processing but has not previously been considered part of the reading network. We also found meaningful individual differences in the activation of this region: Activity was predicted by an independent measure of the degree to which participants use semantic knowledge to read. These characteristics are predicted by the connectionist Triangle Model of reading and indicate a key role for semantic knowledge in reading aloud. Premotor regions associated with phonological processing displayed the reverse characteristics. Changes in the functional connectivity of the reading network during irregular word reading also were consistent with semantic recruitment. These data support the view that reading aloud is underpinned by the joint operation of two neural pathways. They reveal that (i) the ATL is an important element of the ventral semantic pathway and (ii) the division of labor between the two routes varies according to both the properties of the words being read and individual differences in the degree to which participants rely on each route.