Drug shortages continue to pose a significant threat to public health and safety. Drug shortages not only worsen patient outcomes, but also significantly burden healthcare systems with additional costs. This study aimed to assess community pharmacy staff knowledge, opinion, and practice toward drug shortages in Saudi Arabia from November 2019 to March 2020. This was a cross-sectional study carried out among 1,008 community pharmacists from Saudi Arabia using a validated, self-administered and Internet-based survey. Analysis was done using chi square and fisher exact tests. Most participants were males (97.2%), less than 30 years old (48.1%), and non-Saudi citizens (94.4%), and 72.0% had good knowledge of drug shortages (score = 4-5). Around 36.0% reported that it takes 1-3 days to receive a response to the shortage report. There was a statistically significant association between the professional level of the community pharmacists and their opinion about reporting drug shortages (P < .05). Most community pharmacies (56.2%) did not receive any notification about drug shortages. In conclusion, most community pharmacists are knowledgeable and have good practice regarding drug shortages, but their opinions about drug shortages differ according to each pharmacy reporting policy.