A micromachined thermopile infrared sensor is designed and optimized with high detective sensitivity in the article. A matched chopper operational amplifier with good linearity is implemented for signal processing. Optimizations of the sensor’s structure are proposed by the adjustment of the length of the thermocouple pairs and the filling of the back-etched cavity based on the adopted thermocouple materials. A passivation layer is implemented to minimize the flicker noise of the sensor. Based on the requirement of the optimized thermopile sensor system, both the flicker noise and the low-frequency noise of the system are suppressed for achieving high sensitivity. The chopper operational amplifier circuit with a single-ended closed-loop diagram is specifically designed for signal amplification and noise suppression. The fabricated device shows improved characterizations, with the responsivity of 182.72 V/W, detectivity of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2.47\times 10^{{8}}$ </tex-math></inline-formula> cmHz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> /W, time constant of 10 ms, and total resistance of 270 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\text{k}\Omega $ </tex-math></inline-formula> . The sensitivity of the designed system, including the sensor and the amplifier, is about 15 mV/°C, when the gain is 40 dB and the sensor-target distance is 3 cm. The system shows wide applications in the fields of noncontact temperature measurement and other special applications.