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Background The outbreak of Coronavirus (COVID-19) in Wuhan, China, which began in December 2019, evolved to become a global pandemic. The pandemic, along with the obvious health-related impact, also poses a serious threat to the psychological well-being of individuals and has resulted in significant behavioral changes. We aimed to describe the psycho-behavioral response to this crisis among the population of Karachi, Pakistan, in the month of March 2020. Methods A structured, self-administered questionnaire was constructed, based on previously conducted surveys, assessing the psychological impact and behavioral changes pertaining to COVID-19. Questionnaires were made available online, and were administered to any individual who was a resident of Karachi, during March 2020. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp., Armonk, NY) to identify possible risk factors for psychological and behavioral changes. The responses were compared based on gender, age, and level of education, to find possible statistical correlations using chi-square test. Results This research studied data from 400 participants residing in Karachi, Pakistan. The spread of the virus had resulted in subsequent development of fears in the target population, with the majority of the respondents feeling anxious on a daily basis (62.5%). The participants feared going to marketplaces (88.8%), were concerned for the health of their family members (94.5%), and felt under-confident with the current infection control measures (71%). Significantly elevated levels of fear were noted among people >35 years of age. They were more likely to fear for the safety of their health even at home (p=0.06). Meanwhile, increased levels of anxiety due to use of social media among people below 35 years had resulted in avoidance behaviors (p=0.04). There was a higher tendency for graduates to fear for the safety of their health, even at home (p<0.01). In addition, more than three-fourths of our participants had incorporated changes in their behavior to ensure their safety i.e. reduced physical contact (86.5%) and visits to healthcare facilities (74.5%), canceled plans (84.5%), and washing hands more often (87%). Conclusion Our study highlighted the increased anxiety levels that an individual experienced on a regular basis regarding their health, the health of their peers, certain avoidance behaviors as a result of the disease, and behavioral changes of the concerned population. Besides calling attention to this worrisome situation, we also tried to list possible solutions to avert any future distress that may ensue as a result. Hopefully, our study will help the concerned authorities to take measures in order to alleviate the psychological and behavioral impact of COVID-19.