Hydrokinetic turbines extract energy from free-flowing water, such as river streams and marine currents. For river applications, the typical deployment location is highly space-constrained due to both the nature of the river (i.e., its natural width and depth) and the other usages of the river. Therefore, a modified design of a conversion device is desired to accommodate these space limitations. The objective of this work is to derive optimum design criteria for a coaxial horizontal axis hydrokinetic turbine system utilizing both numerical and experimental approaches. Single-turbine systems configured with different sizes of untwisted untapered blades were numerically studied to obtain the optimum solidity and to examine the blockage effects on the various-solidity rotors. The numerical modeling was, then, extended to analyze the performance of the coaxial multi-turbine system (equipped with optimum-solidity rotors) and characterize its ambient flow. The numerically predicted power outputs were validated against those measured with torque and rotational speed sensors in a water tunnel for both single-turbine and multi-turbine systems. Particle image velocimetry was also utilized to evaluate the wake structure and validate the numerical results of the flow characteristics. The optimum-solidity for the single-turbine system was found to be 0.222 48. An optimum-solidity three-turbine axial system can increase power output by 47% when compared to an optimum-solidity single-turbine system. Increasing the number of rotors from three to five only enhanced efficiency by about 4%. The study of wake structures behind a three-turbine system showed that the highest velocity deficit occurs behind the second rotor rather than the third rotor.