This study aims to optimize the design parameters of a vertical axis wind turbine using design of experiments (DOE). Response surface methodology combined with desirability optimization was used to optimize multiple parameters such as the chord length, number of blades, aspect ratio, and pitch angle. The range of contributing parameters was selected using one factor at a time (OFAT) approach, and the performance parameters were evaluated by applying the double multiple streamtube theory. Datasets retrieved from the Q-Blade open-source software were employed in the DOE to determine the optimal configurations. Based on response surface investigation, a quadratic model was established and the accuracy of the model was determined by applying analysis of variance, goodness of fit, normal plot of residuals, and R-squared values. The optimized chord length, number of blades, pitch angle, and aspect ratio were 0.546 m, 03, −2.82°, and 0.808, respectively. The maximum power coefficient of 0.45 was obtained at a tip speed ratio of 3 from the optimized design parameters. The analysis revealed an increase of approximately 8.43% in the maximum power coefficient of the proposed wind turbine. A 3D unsteady computational fluid dynamics model along with Reynolds-Averaged Navier-Stokes equations were utilized to verify the obtained results, and a maximum difference of less than 1.5% was found. A standard H-rotor Darrieus configuration obtained from the OFAT approach was also tested at different wind speeds for comparison. The analysis revealed that when the wind speed was less than 3.85 m/sec, the standard Darrieus produced no power; however, the self-starting speed of the optimized VAWT was as low as 3.22 m/sec. This novel design methodology provides guidelines for obtaining optimum design configurations and can help in achieving high-fidelity analysis in the early design phase.