Repetitive overhead throwing may result in overuse injuries and a change in the pitching mechanics of a baseball pitcher. Accordingly, the purpose of this study is to quantify the changes in the muscle strength and pitching motion kinematics in the late-innings stage of a baseball game. Sixteen healthy baseball pitchers (16.77 ± 0.73 years) recruited from a high school, which won the National High School Baseball Championship in Taiwan in 2011; each performed 100 pitches in a bullpen throwing session. Isometric muscle strength measurements and joint kinematic data were obtained before and after the throwing session. The mean Borg's Rating of Perceived Exertion index was found to have a value of 14.14, indicating a medium-to-large degree of perceived tiredness. The results showed that the ball velocity and horizontal abduction angle decreased significantly as the pitchers became tired. Moreover, the upper torso forward tilt and knee flexion angle both increased significantly at the moment of ball release. Finally, the muscle strength of the upper extremity remained decreased 2 days after the bullpen throwing session. Overall, the results suggest that an adequate amount of rest and specific strengthening programs for the shoulder external rotator, shoulder internal rotator, shoulder flexor, shoulder extensor, shoulder adductor, and shoulder abductor muscles are recommended to the coaches and for adolescent baseball pitchers. In addition, the changes in pitching mechanics noted in this study should be carefully monitored during the course of a baseball game to minimize the risk for overuse injuries.