CO2 laser cutting is an advanced processing technology, which can, according to the computer-aided design graphics, cut a variety of shapes in the surfaces of many polymer sheets. This work aims to analyze the effect of laser power, scanning speed, and processing times on the surface roughness of polymethyl-methacrylate microchannels with CO2 laser LCJG-1290 cutting process. There are several experiments designed by us, and the results were analyzed by orthogonal experimental method. Finally, optimal power, scanning speed, and processing times were obtained, and in the optimal case, the arithmetical mean roughness (Ra) can reach as small as 110 nm.