This study was conducted to identify the status and determinants of male and female youth participation in selected livelihood activities, development programs and interventions in agro-pastoral areas of Oromia regional state, Ethiopia. A cross-sectional research design and mixed methods research approach were employed. A multi-stage random sampling strategy was followed to select four agro-pastoral Woredas (A ‘Woreda’ is an administrative unit equivalent to a District), 12 Kebeles (A ‘Kebele’ is the smallest administrative unit in Ethiopia. A Woreda/District consists of several Kebeles) and 398 youth aged 15–29 years for a face-to-face interview. Data were analysed through descriptive and inferential statistics and an econometric model (Logistic regression) estimation. We found that whereas male youth had better access to land, participation in extension/advisory services and Farmers’ Training Centers (FTCs), agricultural training, and NGOs, female youth had better participation in non-/off-farm livelihood activities and Productive Safety Net Program (PSNP). Our findings indicated that lack of access to financial resources, limited access to land, poor extension and rural advisory services, limited skills development programs and mentorship were key factors affecting youth participation. Other factors include: targeting criteria, discrimination (e.g. on the basis of gender, social structure), cumbersome organizational procedures and requirements, limited availability and capacity of supporting organizations, poor infrastructural developments, mismatch between needs and services provided, conflict, and climate-induced shocks and uncertainties. To overcome these challenges, local and regional governments and their development partners operating in the area should implement a multi-stakeholder, participatory, co-design and development of programs, projects and interventions to enhance collaboration, youth engagement and benefit. Investments in capacity-building and alternative income-generating activities, entrepreneurship education and business skills training are also important.