Microfluidic channels are typically fabricated in polydimethylsiloxane (PDMS) using a combination of photolithography and soft lithography. Photolithography, while ubiquitous in the fabrication of microfluidic devices, generally requires skilled technicians, expensive chemicals, and specialized equipment. This manuscript describes a simple method for the fabrication of masters for use in soft lithography that is based on combining thermoplastic “building blocks” using thermal “welding.” This approach is applicable to the fabrication of an array of devices that possess many of the basic functionalities (e.g., droplet generation, mixing, and splitting) required in microfluidics. In addition to these systems, which are routinely fabricated using photolithographically produced masters, this manuscript describes how thermoplastic building blocks can be stacked, assembled, and replicated to fabricate microfluidic devices with channel crossings and/or channels of variable cross-sectional height—geometries that normally require multiple steps of photolithography. The methods described here enable a range of scientists of varying expertise to prototype a variety of functional microfluidic devices easily and rapidly, even when access to traditional fabrication techniques or time is limited, or when an optimized design is not available.