Antibiotics are commonly reported as being substandard or falsified in low- to middle-income countries, having potential to contribute to the development of antimicrobial resistance and drug-resistant infections. Amoxicillin, used to treat a number of infections and listed by the WHO as an essential medicine, presented as a good drug candidate for this study. We aimed to measure the prevalence of substandard and falsified amoxicillin oral products (tablets, capsules, and suspensions) in the National Capital District of Papua New Guinea (PNG). These oral products were surveyed in 2018 and 2019 from retail pharmacies, private and public health facilities, and the Area Medical Store, representing more than 90% of licensed medicine outlets. The product packaging was visually inspected, and the samples were analyzed for amoxicillin content using a validated high-performance liquid chromatography method. Although no falsified products were identified, 15% of the 190 products analyzed contained substandard amounts of amoxicillin. Quality varied with the dosage form (P = 0.002), with capsules exhibiting the lowest incidence of substandard content (4% in 2019) and tablets collected in 2018 experiencing the highest failure rate (50%). Suspension (40%) quality was compromised by failure to achieve homogeneity on reconstitution. A higher incidence of substandard content (P = 0.002) was associated with one major retail group. Routine testing of medicines by resource-poor countries is often unachievable, leading to the circulation of poor quality drugs, which is a global public health concern. Our study highlighted that substandard amoxicillin oral products are indeed prevalent in the NCD of PNG.