Controllable integration of two or more functional components is one of the most convenient and effective ways to obtain composite advanced materials with collective properties and improved performance. In this work, in combination with organic single crystals and metal–organic frameworks (MOFs), a novel 1D well‐defined core–shell heterostructure with single copper phthalocyanine (CuPc) ribbon cores coated with a uniform isoreticular MOF‐3 (IRMOF‐3) shell is successfully constructed. Impressively, thanks to performance the integration and synergy of the CuPc cores and the IRMOF‐3 shells, the sensor devices based on such single heterostructures exhibit outstanding selectivity for NH3 detection at ≈60% relative humidity at room temperature, the current response of which to NH3 is around 34–265 times the magnitude of response to ten potential interfering gases even in the case of the 1:100 concentration ratio of NH3 (5 ppm) and the interfering gases (500 ppm). Moreover, the detection limit of such CuPc@IRMOF‐3 sensors toward NH3 is estimated to be 52 ppb (signal to noise ratio = 3) based on 11 blank determinations, and good stability and reusability can also be achieved. This work highlights that the integration of organic single crystals and MOFs into well‐defined structures offers a new opportunity for high‐performance gas sensors.