Background Healthcare workers (HCWs) stand the risk of acquiring infection directly, while attending to patients or indirectly while handling and testing patient specimens. Considering this, the present study was planned to assess Personal Protective Equipment (PPE) breaches and exposures among HCWs working in COVID-19 wards/ screening areas and to evaluate their COVID-19 positivity rates post-exposure concerning the level of exposure, type of PPE breach, and the cadre of HCWs exposed in COVID-19 wards. Methods This retrospective cross-sectional study involved the analysis of all instances of PPE breaches which occurred during a period of nine months from June 2020 to February 2021 at a tertiary care level hospital in Central India. The analysis included all exposures involving any cadre of HCWs that occurred while handling the patients or while doffing the contaminated PPE in COVID -19 wards. Results A total of 347 PPE breaches were analyzed from the available records of the Hospital Infection Control team repository. Amongst the 347 breaches, 268 (77.2%) were classified as low-risk exposures and 79 (22.8%) as high-risk exposures. Cadre wise distribution of high and low-risk exposures revealed that, PPE breaches occurred most commonly in the category of nursing officers (n = 174, 50.1%). Among all of the breaches, 15.2% of high-risk exposures and 2.6% of low-risk exposures resulted in COVID-19 positivity with a cumulative positivity of 5.4%. Collectively, non-mask related breaches accounted for the majority (63.2%) of the positive COVID-19 cases. Conclusion Appropriate use of PPE by HCWs is vital for their protection. However, breaches in the use of PPE may occur while managing COVID-19 patients due to physical and mental exhaustion among HCWs resulting from work overload. Early identification and appropriate management of HCWs with high-risk exposures can help prevent transmission to other hospital staff and patients, thus preserving resources and workforce.