Flexible stress sensor arrays, comprising multiple flexible stress sensor units, enable accurate quantification and analysis of spatial stress distribution. Nevertheless, the current implementation of flexible stress sensor arrays faces the challenge of excessive signal wires, resulting in reduced deformability, stability, reliability, and increased costs. The primary obstacle lies in the electric amplitude modulation nature of the sensor unit’s signal (e.g., resistance and capacitance), allowing only one signal per wire. To overcome this challenge, the single-line multi-channel signal (SLMC) measurement has been developed, enabling simultaneous detection of multiple sensor signals through one or two signal wires, which effectively reduces the number of signal wires, thereby enhancing stability, deformability, and reliability. This review offers a general knowledge of SLMC measurement beginning with flexible stress sensors and their piezoresistive, capacitive, piezoelectric, and triboelectric sensing mechanisms. A further discussion is given on different arraying methods and their corresponding advantages and disadvantages. Finally, this review categorizes existing SLMC measurement methods into RLC series resonant sensing, transmission line sensing, ionic conductor sensing, triboelectric sensing, piezoresistive sensing, and distributed fiber optic sensing based on their mechanisms, describes the mechanisms and characteristics of each method and summarizes the research status of SLMC measurement.