Stretchable strain sensors with high sensitivity or gauge factor (GF), large stretchability, and long-term durability are highly demanded in human motion detection, artificial intelligence, and electronic skins. Nevertheless, to develop high-sensitive sensors without sacrificing the stretchability cannot be realized using simple device configurations. In this work, an acid-interface engineering (AIE) method was proposed to develop a stretchable strain sensor with high GF and large stretchability. The AIE generates a layer of SiO x at the interface between the carbon nanotube (CNT) film and Ecoflex, playing a key role in enhancing the sensor's GF. Compared to devices without AIE (GF = 2.4), the ones with AIE are significantly improved. At an AIE time of 10 min, the GF up to 1665.9 is achieved without sacrificing the stretchability (>100%). The AIE-generated cracks are found to modulate the electrical behaviors and enhance the GFs of sensors with AIE through the crack-induced rapid reduction in the electrical conduction pathway, which is manipulated by the CNTs bridging over the cracks. The device with AIE proves its high mechanical durability through a cycling test (>10 000 cycles) at a high strain up to ∼80%, further paving its practical applications in various human motion detections.