Background: The COVID-19 pandemic has exacerbated mental health challenges among medical students, already a vulnerable group to mental health disorders. Recent evidence underscores a significant rise in anxiety, depression, and stress among this demographic globally, necessitating a deeper understanding of their mental health status and effective interventions. Objective: This study aims to assess the socio-demographic profile, prevalence rates of depression, anxiety, and stress, as well as coping strategies employed by medical students during the COVID-19 pandemic, with a focus on identifying effective interventions for managing their mental health crises. Methods: A cross-sectional study was conducted among 1st to 4th year MBBS students at ACSR Government Medical College, Nellore, during August and September 2020. Data were collected online using Google Forms, incorporating demographic details and the Depression, Anxiety, and Stress Scale (DASS-21). Descriptive statistics and chi-square tests were utilized for data analysis. Results: The study included 400 participants, 57% of whom were female, with a mean age of 23 ± 2 years. Significant proportions reported experiencing depression (20.2%), anxiety (13%), or stress (51.3%), with notable rates of past psychiatric symptoms. Coping mechanisms included video chatting (35%) and online entertainment (32.2%), while professional help utilization was low (5.5%). COVID-19 repercussions extended beyond mental health, impacting various facets of daily life. Conclusion: This study found various mental health challenges faced by medical students during the pandemic, emphasising the need for ongoing monitoring and psychological support. Additionally, a low rate of seeking professional help was found. Early training in handling pandemic-like situations and mental health is recommended. However, further research is necessary to track mental health progression and ensure accurate diagnosis through individual clinical assessments.