We used functional magnetic resonance imaging to study the pitch-calling behavior of baseball umpires with varying experience, with a particular interest in understanding the pitcher handedness effect. Expert and intermediate umpires were recruited and asked to make ball/strike calls on videotaped pitches of left- and right-handed pitchers and rate their certainty for the call while undergoing scanning. Behavioral results replicated previous findings that expert umpires were more certain but not more accurate or quicker than intermediate umpires, suggesting that umpires learn to project confidence to maintain control of the game as sports officials. Both expert and intermediate umpires were less accurate when judging the left-handed pitcher than the right-handed pitcher (particularly with longer reaction times and less uncertainty for ball pitches), possibly due to their lower familiarity with rarely encountered left-handed pitchers. The umpires greatly engaged the action observation network, cerebellum, and caudate when making correct calls, and these activations were comparatively weaker when calling left-handed pitches, implying their less effective perceptual processing of the visual information details of the left-handed pitcher. The lower activity in the right premotor cortex for ball pitches from the left-handed pitcher further implies the umpires’ poorer predictive processing of the pitching action and baseball trajectory of the left-handed pitcher than the right-handed one, particularly for ball pitches. Our findings shed light on the influence of pitcher handedness on the pitch-calling behavior of baseball umpires and extend the current understanding of the perceptual and decision-making behavior of baseball umpires (sports officials).