Our long-term goal is to understand the extent to which motor impairments reported in autism may be related to abnormalities of brain function. We previously described a robotic joystick and video game system that allows us to record functional magnetic resonance images (FMRI) while adult humans make goal-directed wrist motions. We anticipated several challenges in extending this approach to studying goal-directed behaviors in children with autism spectrum disorders (ASD) and in typically developing (TYP) children. In particular we were concerned that children with autism may express increased levels of anxiety as compared to typically developing children due to the loud sounds and small enclosed space of the MRI scanner. We also were concerned that both groups of children might become restless during testing, leading to an unacceptable amount of head movement. Here we evaluated both the extent to which autistic and typically developing children exhibit anxiety during our experimental protocol and their ability to comply with task instructions. Our experimental controls were successful in minimizing group differences in drop-out due to anxiety. Kinematic performance and head motion also were similar across groups. Both groups of children engaged cortical regions (frontal, parietal, temporal, occipital). In addition, the ASD group exhibited task-related correlations in subcortical regions (cerebellum, thalamus), whereas correlations in the TYP group did not reach statistical significance in subcortical regions. Four distinct regions in frontal cortex showed a significant group difference such that TYP children exhibited positive correlations between the hemodynamic response and movement onset, whereas children with ASD exhibited negative correlations. These findings demonstrate feasibility of simultaneous application of robotic manipulation and functional imaging to study goal-directed motor behaviors in autistic and typically developing children.