Despite progress in improving antiretroviral therapy (ART) for people with HIV in Malawi, the burden of HIV infections and HIV treatment outcomes among key populations is suboptimal. Client-centered differentiated service delivery approaches may facilitate addressing HIV prevention and treatment needs of key populations in Malawi. Methods De-identified program data routinely collected as part of the LINKAGES project–Malawi were assembled from October 2017 to September 2019. HIV case finding was compared across different testing modalities for each population. Poisson regression was used to estimate the association between testing modalities and ART initiation. Results Of the 18 397 people included in analyses, 10 627 (58%) were female sex workers (FSWs), 2219 (12%) were men who have sex with men (MSM), and 4970 (27%) were clients of FSWs. HIV case finding varied by modality and population, with index testing and enhanced peer outreach demonstrating high yield despite reaching relatively few individuals. FSWs who tested positive through risk network referral testing were more likely to initiate ART within 30 days compared with those who tested positive through clinic-based testing (adjusted risk ratio [aRR], 1.50; 95% CI, 1.23–1.82). For MSM, index testing (aRR, 1.45; 95% CI, 1.06–2.00) and testing through a drop-in center (aRR, 1.82; 95% CI, 1.19–2.78) were associated with 30-day ART initiation. Conclusions These data suggest that differentiated HIV testing and outreach approaches tailored to the needs of different key populations may facilitate improved ART initiation in Malawi. Achieving 0 new infections by 2030 suggests the need to adapt treatment strategies given individual and structural barriers to treatment for key populations with HIV in high-prevalence settings.