HIV-related stigma and discrimination (S&D) in healthcare settings represents a potent barrier to achieving global aims to end the HIV epidemic, particularly in Southeast Asia (Cambodia, Lao People’s Democratic Republic, Thailand and Vietnam). Evidence-based approaches for measuring and reducing S&D in healthcare settings exist, but their incorporation into routine practice remains limited, in part due to a lack of attention to how unique organisational practices—beyond the knowledge and attitudes of individuals—may abet and reinforce S&D. Application of a quality improvement (QI) approach in which facilities leverage routine measurement of S&D among healthcare workers and people living with HIV, team-based learning, root cause analysis, and tests of change offers a novel means through which to address S&D in local contexts and develop interventions to address individual-level and organisation-level drivers of S&D. To support the adoption of a QI approach to S&D reduction, the Southeast Asia Stigma Reduction QI Learning Network was launched with Ministries of Health from Cambodia, Lao PDR, Thailand and Vietnam, to co-develop strategies for implementing QI activities in participating facilities. Since the inception of Network activities in 2017, Ministry-led QI activities to address S&D have been implemented in 83 facilities and 29 provinces across participating countries. Moreover, 27 strategies and interventions have been tested to date and are being evaluated for scale up by participating facilities, spanning multiple drivers and organisational domains. Lessons learned through Network activities offer national-level and facility-level HIV programmes best practices for implementing a QI approach to S&D reduction.