Despite its widespread use to measure functional lateralization of language in healthy subjects, the neurocognitive bases of the visual field effect in lateralized reading are still debated. Crucially, the lack of knowledge on the nature of the visual field effect is accompanied by a lack of knowledge on the relative impact of psycholinguistic factors on its measurement, thus potentially casting doubts on its validity as a functional laterality measure. In this study, an eye-tracking-controlled tachistoscopic lateralized lexical decision task (Experiment 1) was administered to 60 right-handed and 60 left-handed volunteers and word length, orthographic neighborhood, word frequency, and imageability were manipulated. The magnitude of visual field effect was bigger in right-handed than in left-handed participants. Across the whole sample, a visual field-by-frequency interaction was observed, whereby a comparatively smaller effect of word frequency was detected in the left visual field/right hemisphere (LVF/RH) than in the right visual field/left hemisphere (RVF/LH). In a subsequent computational study (Experiment 2), efficient (LH) and inefficient (RH) activation of lexical orthographic nodes was modelled by means of the Naïve Discriminative Learning approach. Computational data simulated the effect of visual field and its interaction with frequency observed in the Experiment 1. Data suggest that the visual field effect can be biased by word frequency. Less distinctive connections between orthographic cues and lexical/semantic output units in the RH than in the LH can account for the emergence of the visual field effect and its interaction with word frequency.