The objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC). Whole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N = 227, aged 18–76 years old, male/female = 99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index and connectivity density index utilizing the convolutions of the cross-correlation histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately. With the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyri, posterior cingulate cortex (PCC), right insula and inferior parietal lobule of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: (1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; (2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; and (3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age. The proposed QDA framework can produce threshold-free and voxel-wise RFC metrics from R-fMRI data. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging.