In nanotechnology, understanding the effect of interfaces and defects becomes critically important in determining a material's properties and device performance. Many one-dimensional and two-dimensional materials exhibit excellent physical, electrical, thermal, and optical properties, making them highly desirable for a wide array of applications. However, their low dimensionality also means their performance can be susceptible to defects in the material and the interfaces they form with other device components. Carbon nanotubes are often used in sensing applications, typically, in a field-effect transistor configuration (CNTFET). The interface between the contact electrode metal and the nanotube forms a Schottky barrier, which plays an important role in both transistor and sensor characteristics. Modifications to this interface by the environment can modulate the barrier and produce a change in device characteristics. Transistor operation can also be modified by the presence of defects in the carbon nanotube sidewall structure. This paper explores how defects in single-wall carbon nanotubes can affect the sensing mechanism of CNTFET gas sensing devices. Gas exposure measurements were performed on as-grown near pristine (low defect) nanotube devices and compared with plasma irradiated, highly defective nanotube devices. By utilizing selective passivation to isolate structural components that contribute to the sensing mechanism, the study shows that the presence of defects, and their relative densities, has a critical role in gas sensing performance. Recognizing the presence of these defects, even in as-grown nanotubes, can help reconcile seemingly contradictory results in the literature regarding the gas sensing mechanism. This work represents an important step toward understanding the effect of both interfaces and defects for carbon nanotube sensor development.