Micropipette-based thermocouples provide the advantage of a high tip diameter-to-length aspect ratio allowing the maintenance of a reference temperature crucial for accurate thermal sensing in microdomains. The research efforts in this field strive to achieve high thermoelectric power (voltage change per unit temperature change) while minimizing the sensing area, a pair of tasks that is by nature contradictory and thus, challenging. Herein, the design and fabrication of a carbon-based micropipette thermal sensor are described. A novel manufacturing method and set of materials are used to overcome the reduction in thermoelectric performance associated with small sensor sizes. A glass micropipette is utilized as a template in a chemical vapor deposition process to form a carbon layer in the lumen of the pipette. This carbon micropipette then serves as a scaffold on which gold and nickel are deposited, enabling the device to function as a thermocouple. This low-cost fabrication process results in a thermocouple with a sub-500 nm tip. The response of the thermocouple was characterized and demonstrated good repeatability in a temperature range of 0 to 60 °C. The unique material selection provided a thermoelectric power of 14.9 μV·K−1, a significant improvement (68%) relative to other micropipette-based thermocouples.