Defects and strain control in AlxGa1-xN/GaN multiple quantum wells (MQWs) for intersubband transitions (ISBTs) at atmospheric window grown on GaN/sapphire templates by metal-organic chemical vapor deposition have been investigated adopting strain modulation technique using AlN/GaN superlattices (SLs) interlayer. It is found that cracking in the MQWs can be effectively avoided adopting AlN/GaN SLs interlayer. It is demonstrated that AlN/GaN SLs interlayer acts as a flexible layer and relieves most of the tensile strain through buried microcracks in AlN/GaN SLs interlayer. The intersubband absorptions at 3.6–4.1 μm wavelength region have been observed on the crack-free AlxGa1-xN/GaN MQWs. Our results open up prospects to realize crack-free and high quality AlxGa1-xN/GaN MQWs on GaN/sapphire templates for ISBTs devices at 3–5 μm atmospheric window.