Although there are many eye-movement studies focusing on natural sentence reading and functional magnetic resonance imaging research on reading with serial visual presentation paradigms, there is a scarcity of investigations into the neural mechanism of natural sentence reading. The present study recruited 33 adults to read unspaced and spaced Chinese sentences with the eye tracking and functional magnetic resonance imaging data recorded simultaneously. By using fixation-related functional magnetic resonance imaging analysis, this study showed that natural reading of Chinese sentences produced activations in ventral visual, dorsal attention, and semantic brain regions, which were modulated by the properties of words such as word length and word frequency. The multivoxel pattern analysis showed that the activity pattern in the left middle temporal gyrus could significantly predict the visual layout categories (i.e. unspaced vs. spaced conditions). Dynamic causal modeling analysis showed that there were bidirectional brain connections between the left middle temporal gyrus and the left inferior occipital cortex in the unspaced Chinese sentence reading but not in the spaced reading. These results provide a neural mechanism for the natural reading of Chinese sentences from the perspective of word segmentation.