Aims: The aim of current study is to find out the prevalence of depression in doctors in different hospitals of Karachi and its association with lifestyle, the field of specialty and coping mechanisms. Place and Duration of Study: The sample was collected from 10 different hospitals of Karachi, in a period of one Year i.e., March 2019 to February 2020. Methodology: A descriptive cross-sectional study design using non-probability consecutive type of sampling technique was used. Sample size was calculated at 95% confidence interval and was found to be 368. The sample was classified in two broader categories Surgery & Allied and Medicine & Allied. For identification of depression level, Public Health Questionnaire (PHQ-9) was used. A 28-item questionnaire Brief COPE was used to asses coping mechanisms. Results: In total 400 forms were used for data analysis. The mean age of doctors was 35 ± 4 years, 65% were males while 35% were females, there was a statistically significant association of female gender with depression. Chi-Square was applied to determine the association of depression and departments and it was found to be highly significant with a P < .001. Highest level of depression was found in Orthopedics and Psychiatry departments followed by Surgery and Gynecology. While Otolaryngology was the least depressed department. Chi-square was applied and a statistically significant association of low monthly income and depression with a p-value of 0.02. In Surgery and allied there was a statistically significant association of depression with extensive working hours and lack of facilities with a p-value of 0.01 and 0.04. While in Medicine and allied there was a statistically significant association of depression with a harsh attitude of seniors and an uncomfortable working environment with a p-value of 0.02 and 0.03. A linear regression model comparing depression and its associations with coping strategies was applied. Conclusion: Our study shows that depression is present in a vast majority of doctors from multiple specialties. Various risk factors for depression have also been identified so appropriate coping strategies should be formulated to deal with it.