Codling moth (Cydia pomonella L.) is a very important pest in apple, pear, and walnut orchards worldwide, including the USA. Cydia pomonella granulovirus (CpGV) is used to control codling moth in organic and conventional production. Due to increasing codling moth infestations from organic apple orchards in Washington State, USA, five codling moth colonies (WA1-WA5) were screened for their susceptibility relative to the isolate GV-0001, the main active ingredient of Cyd-X®, using a discriminating concentration of 6 × 104 OB/mL. Compared to a susceptible laboratory colony, the observed results indicated that GV-0001 lacked efficacy against codling moth colony WA3. It was confirmed that WA3 was the first case of codling moth resistance to CpGV in the USA. Further testing of WA3 was performed on a range of CpGV isolates and a lack of efficacy was observed against additional isolates. However, three newly developed CpGV preparations can efficiently infect larvae from the resistant colony WA3. Our results suggest that there is an urgent need to monitor the situation in the USA, aiming to prevent the emergence or spread of additional codling moth populations with CpGV resistance. Strategies to sustain the efficacy of codling moth control using novel CpGV formulations need to be developed.