Simultaneous investigation of kerf quality and fume emissions during laser cutting process is essential to achieve efficient and hygienic cutting process. In this study, an experimental investigation on process factors of CO2 laser cutting (CLC) of polyvinyl chloride (PVC) sheets has been carried out followed by an optimization study to enhance the kerf geometry and reduce the emitted harmful fumes. Laser power, transverse cutting speed, and sheet thickness have been considered as the process factors. The kerf geometry has been measured using optical microscope. The emitted fumes are considered to be proportional to the generated kerf volume. An L9 experimental design plan was designed using Taguchi method, and the results were evaluated using analysis of variance (ANOVA). Second-order regression models have been developed to correlate the input parameters to the process responses. Genetic algorithm (GA) was implemented to obtain the optimum process parameters that should be used to minimize the kerf volume and consequently the emitted fumes. A significant decrease in kerf volume has been obtained using the optimum process parameters. Confirmation experiments have been conducted to verify the accuracy of the proposed approach. The proposed optimization method shows a considerable decrease in the kerf volume and the emitted fumes, especially for large sheet thicknesses. The emitted fumes can be reduced by about 39% and 61% for sheet thickness of 7 mm and 10 mm, respectively, by applying the optimum cutting parameters obtained from this study.