Following the implementation of the Movement Control Order (MCO) during the coronavirus disease 2019 (COVID-19) pandemic, academicians from the universities in Malaysia needed to ensure that the quality-of-service delivery to the stakeholders is undisturbed by adopting new challenging norms. This compromises the work-life balance (WLB), causes more stress and potentially affects their quality of life (QoL). This study investigates how perceived stress (PS) impacts the QoL of Malaysian academicians during the COVID-19 pandemic, focusing on the mediating role of WLB. Academics working in Malaysia during COVID-19 pandemic. A cross-sectional study, using a voluntary response sampling method, was conducted among 417 academicians from universities in Malaysia in September 2021. A self-reported online questionnaire, measuring PS, WLB and QoL, was distributed. The QoL scored a mean of 50 (standard deviation [s.d.] = 9.84), PS scored a mean of 24.26 (s.d. = 8.19) and WLB had a mean score of 51.12 (s.d. = 18.73). Work-life balance was a significant mediator of PS and QoL (β = -0.43, 95% confidence interval [CI] = -0.52 to -0.35, p = 0.0001). Perceived stress was a significant predictor of WLB (β = 1.62, p = 0.0001). Institutions should consider implementing flexible working arrangements, and providing workshops on crisis management, time management, and resilience. Stress coping methods are recommended for enhancing WLB among academicians. This study contributes to the pool of evidence to support intervention strategies and policy recommendations aimed to enhance well-being.