Novelty seeking (NS) and harm avoidance (HA) are two major dimensions of temperament in Cloninger's neurobiological model of personality. Previous neurofunctional and biological studies on temperament dimensions of HA and NS suggested that the temperamental traits have significant correlations with cortical and subcortical brain regions. However, no study to date has investigated the functional network modular organization as a function of the temperament dimension. The temperament dimensions were originally proposed to be independent of one another. However, a meta-analysis based on 16 published articles found a significant negative correlation between HA and NS (Miettunen et al., 2008). Based on this negative correlation, the current study revealed the whole-brain connectivity modular archi- tecture for two contrasting temperament groups. The k-means clustering algorithm, with the temperamental traits of HA and NS as an input, was applied to divide the 40 subjects into two temperament groups: ‘high HA and low NS’ versus ‘low HA and high NS’. Using the graph theoretical framework, we found a functional segregation of whole brain network architectures derived from resting-state functional MRI. In the ‘high HA and low NS’ group, the regulatory brain regions, such as the prefrontal cortex (PFC), are clustered together with the limbic system. In the ‘low HA and high NS’ group, however, brain regions lying on the dopaminergic pathways, such as the PFC and basal ganglia, are partitioned together. These findings suggest that the neural basis of inhibited, passive, and inactive behaviors in the ‘high HA and low NS’ group was derived from the increased network associations between the PFC and limbic clusters. In addition, supporting evidence of topological differences between the two temperament groups was found by analyzing the functional connectivity density and gray matter volume, and by computing the relationships between the morphometry and function of the brain.