The growing adoption of unmanned aerial vehicles (UAVs) for tasks such as eCommerce, aerial surveillance, and environmental monitoring introduces the need for new safety mechanisms in an increasingly cluttered airspace. In our work we thus emphasize safety issues that emerge at the intersection of infrastructures responsible for controlling the airspace, and the diverse UAVs operating in their space. We build on safety assurance cases (SAC) - a state-of-the-art solution for reasoning about safety - and propose a novel approach based on interlocking SACs. The infrastructure safety case (ISAC) specifies assumptions upon UAV behavior, while each UAV demonstrates compliance to the ISAC by presenting its own (pluggable) safety case (pSAC) which connects to the ISAC through a set of interlock points. To collect information on each UAV we enforce a “trust but monitor” policy, supported by runtime monitoring and an underlying reputation model. We evaluate our approach in three ways: first by developing ISACs for two UAV infrastructures, second by running simulations to evaluate end-to-end effectiveness, and finally via an outdoor field-study with physical UAVs. The results show that interlocking SACs can be effective for identifying, specifying, and monitoring safety-related constraints upon UAVs flying in a controlled airspace.