BACKGROUND Functional Magnetic Resonance Imaging (fMRI) has the potential to provide non-invasive functional mapping of the brain with high spatial and temporal resolution. However, fMRI independent components (ICs) must be manually inspected, selected, and interpreted, requiring time and expertise. We propose a novel approach for automated labeling of fMRI independent components by establishing their characteristic spatio-functional relationship. METHODS The approach identifies 9 Resting State Networks and 45 independent components and generates a functional activation feature map that quantifies the spatial distribution, relative to an anatomical labeled atlas, of the z-scores of each IC across a cohort of 176 subjects. The cosine-similarity metric was used to classify unlabeled independent component based on the similarity to the spatial distribution of activation with the pre-generated feature map. The approach was tested on three fMRI datasets from the 1000 functional connectome project, consisting of 280 subjects, that were not included in feature map generation. RESULTS The results demonstrate the effectiveness of the approach in classifying independent components based on their spatial features with an accuracy of better than 95%. CONCLUSIONS The approach significantly reduces expert time and computation time required for labeling independent components while improving reliability and accuracy. The spatio-functional relationship also provides an explainable relationship between the functional activation and the anatomically defined regions.