The study aimed to examine alterations in surface-based amplitude of low-frequency fluctuations (ALFF) and fractional amplitude of low-frequency fluctuations (fALFF) in primary open-angle glaucoma (POAG) patients using resting-state functional magnetic resonance imaging (rs-fMRI), and to investigate their relationships with visual function and molecular profiling. A total of 70 POAG patients and 45 age- and sex-matched healthy controls (HCs) underwent rs-fMRI scans. The differences between POAG and HCs groups were compared by two-sample t-test. Spearman's correlation analyses assessed the relationship between ALFF/fALFF values and ophthalmic parameters. Spatial correlation analysis of the patients-control difference map with brain imaging data further explores underlying neurobiological mechanisms. POAG patients displayed altered brain activity compared to HCs, including decreased ALFF/fALFF in the visual network and increased in the frontoparietal and default mode networks. They exhibited reduced fALFF in the somatomotor network and increased ALFF in the dorsal and ventral attention networks. These changes are linked to neurotransmitter systems, with fALFF particularly associated with the dopamine system. Moreover, the altered ALFF/fALFF in brain regions related to vision and attention - the occipital lobe, temporal lobe, parietal lobe, paracentral lobule, and frontal lobe correlated with ophthalmic examination parameters. Surface-based ALFF/fALFF in POAG decreased in visual processing regions and increased in brain regions related to cognitive control, working memory, and attention. These changes were linked to neurotransmitter distributions important for emotional stability and mental health, potentially informing treatment approaches for POAG patients.