Traditional glass micromachining using laser processing in air would produce many kinds of defects, such as bulges, debris, micro-cracks and scorches. In this article, a poly-dimethylsiloxane (PDMS) protection processing has been presented to reduce the temperature gradient and heat-affected zone (HAZ) to achieve crack-free Pyrex glass machining. A good quality of etched surface which is a clear and much-reduced bulge without crack and scorch is achieved using CO2 laser micromachining at 150 μm thick PDMS protection layer and the laser powers of 10–15 W and scanning speeds of 228–342 mm/s for five passes. The PDMS cover layer benefits feature size and bulge height reduction. The alpha-step measured profile shows that the much reduced bulge height around the rims of channel was about 1.2 μm at 150 μm thick PDMS about 13 times smaller than that in air. The ANSYS software was used to analyze the temperature distribution and thermal stress field of glass micromachining in air without and with PDMS cover layer. The smaller temperature gradient observed in PDMS protection processing has the smaller HAZ and diminishes the crack formation during the laser processing.