For ensuring food demand of the fast growing population in developing countries, quantification of crop yield gaps and exploring production constraints are very crucial. Sorghum is one of the most important climate change resilient crops in the rainfed farming systems of semi-arid tropics. However, there is little information about yield gaps and production constraints. This study aimed at analysing existing yield gaps and exploring major constraints of sorghum production in Southwest Ethiopia. A crop simulation model approach using AquaCrop and DSSAT was used to estimate potential yield and analyse the yield gaps. Model calibration and evaluation was performed using data from field experiments conducted in 2018 and 2019. Sorghum production constraints were assessed using a survey. The actual and water-limited yield of sorghum ranged from 0.58 to 2.51 and 3.6 to 6.47 t/ha, respectively for the period 2003–17. The regional yield gaps of sorghum for the targeted period were 3.02–3.95 t/ha with a mean value of 3.51 t/ha. Majority of respondent farmers considered seasonal rainfall risk (98%), poor soil fertility (86%), lack of improved varieties (78%) and inadequate weed management (56%) as major factors responsible for the existing yield gaps. The mean exploitable yield gap (2.5 t/ha) between water-limited and actual yield showed the level of existing opportunity for improvement in the actual productivity of sorghum. The gaps also call for introduction of proper interventions such as adoption of improved varieties, planting date adjustment, conservation tillage, fertilizer application and on time weed management.