© 2021 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.Potato late blight (Phytophthora infestans (Mont.) De Bary) is the major constraint of potato production in Ethiopia. The field experiment was done at Meket district during 2018 cropping season, to determine appropriate spraying frequency combined with different levels of resistance variety. The experiment had 15 treatments with a combination of three potato varieties (Belete, Gudene, and Jalene) and five spraying frequencies (zero, one, two, three, and four times spray). The experiment was arranged in a randomized complete block design in factorial combination with three replications. The combination of potato varieties and spraying frequencies of Ridomil applications showed statistically significant on the disease, yield, and yield component parameters. The highest disease severity (84.76%) was obtained from untreated Jalene variety. The maximum tuber yield (29.62 t ha −1) was obtained from Belete variety sprayed with two-time spraying. Whereas the lowest tuber yield (12.93 t ha−1) was recorded from untreated Jalene variety. Moreover, the highest (1774.65%) marginal rate of return was obtained from Belete variety treated with one spray. Finally, it is concluded that for moderately resistance one spray, moderately susceptible two sprays and four sprays for susceptible varieties were found better management options and get the highest cost-benefit as compared with other treatment combinations.