Based on primary data collected from 191 farming households cultivating 2 rice crops and 1 sesame crop and 115 farming households cultivating a specialized crop model of 3 rice crops in 2022 in the Mekong Delta, the analysis results indicate that the financial efficiency of the group of farmers farming according to the rotational cropping model of 2 rice crops and 1 sesame crop is 2.38 times higher than the group of farming households following the specialized cropping model of 3 rice crops in the Mekong Delta. Through the random marginal production function and the Cobb-Douglas random marginal profit function, the technical efficiency and economic efficiency of farming households following the rotation model of 2 rice crops and 1 sesame crop were estimated. The estimated results show that the average technical efficiency of the Winter-Spring rice crop, sesame crop, and Fall – Winter rice crop are 81.91%, 81.07%, and 88.95%, respectively. The average economic efficiency of farming households estimated in this study is 73.28% in the sesame crop, 66.06% in the Winter – Spring rice crop, and 60.69% in the Fall – Winter rice crop. This result show that with the level use of existing inputs and techniques, the rice and sesame productivity of farmers has potential to increase further tp achieve maximum productivity and improve technical effiency. The level of economic efficiency of farming households is also likely to increase if the technical efficiency and allocative efficiency of farming households are optimally improved. Based on the research results, some solution to improve the production efficiency of the rice-sesame rotation model in the Mekong Delta have been proposed.