Multilevel inverters (MLI) are popular in high-power applications. MLIs are generally configured to have switches reduced by switching techniques that eliminate low-order harmonics. The selective harmonic elimination (SHE) method, which significantly reduces the number of switching, determines the optimal switching moments to obtain the desired output voltage and eliminates the desired harmonic components. To solve the SHE problem, classical methods are primarily employed. The disadvantages of such methods are the high probability of trapping in locally optimal solutions and their dependence on initial controlling parameters. One solution to overcome this problem is the use of metaheuristic algorithms. In this study, firstly, 22 metaheuristic algorithms with different sources of inspiration were used to solve the SHE problem at different levels of MLIs, and their performances were extensively analyzed. To reveal the method that offers the best solution, these algorithms were first applied to an 11-level MLI circuit, and six methods were determined as a result of the performance analysis. As a result of the evaluation, the outstanding methods were SPBO, BMO, GA, GWO, MFO, and SPSA. As a result of the application of superior methods to 7-, 11-, 15-, and 19-level MLIs according to the IEEE 519—2014 standard, it has been shown that BMO outperforms in 7-level MLI, GA in 11-level MLI, and SPBO in 15- and 19-level MLIs in terms of THD, while in terms of output voltage quality, GA in 7-level MLI, BMO in 11-level MLI, GA and SPSA in 15-level MLI, and SPSA in 19-level MLI come forward.