The purpose of the study was to investigate the relationship between physical fitness variables and playing ability of male handball players in Senior High Schools in the Central Region of Ghana. The population consisted of 960 male handball players in five zones from 64 Senior High Schools in Central Region. Out of this, 156 of the players were purposively sampled for the study. The ages of participants ranged between 15 and 22 years. Data was collected on physical fitness variables and handball playing ability. Mean and standard deviations were calculated for each of the selected variables and compared with normative data. The inter-relationship among the selected physical fitness variables and handball playing ability were calculated using Pearson product-moment correlation. Stepwise method of multiple regression was used to find out which predictor variables had the highest correlation with the criterion variables. The results revealed that physical fitness variables (speed, arm strength, leg strength, flexibility, agility, cardiovascular endurance) had significant relationships with playing ability of handball players in Schools and Colleges in the Central Region of Ghana at p < 0.05. It is therefore recommended that coaches or trainers use data on physical fitness and handball playing ability as criteria for selecting players at the SHS level into their handball teams and also develop their training programmes by emphasising on related physical fitness variables to improve playing performance in handball at the SHS level.