Stem rust is a widespread and destructive wheat disease which reduces yield every year in Meket district. This study was aimed at determining the combination effects of fungicide and varieties against stem rust. The experiment was conducted at Meket district during 2020 main cropping season. The study employed both survey and field experiment. A total of 381 wheat farmer fields were assessed for the prevalence, incidence, and severity of stem rust disease. The field experiment was conducted at the meket district using four wheat varieties (local, kekeba, hiddase, and ogolcho) and three different fungicides (orius, folicur, and tilt) where unsprayed control was included. A total of 16 treatment combinations with three replications were layout in a factorial arrangement in RCBD.SAS version 9.4 was used for data analysis to generate ANOVA table and mean comparisons. The highest disease incidence (74.1%) was recorded in unsprayed plots of local variety followed by hiddase (64.6%), and kekeba (54.2%) varieties, respectively. Whereas, the lowest disease incidence (16%) was occurred on ogolcho variety sprayed with Tilt 250 E.C. The highest infection rate (0.09296unit day-1) and AUDPC value (698.6) were obtained from unsprayed plots of local variety. The lowest infection rate (0.05614 unit day-1) and AUDPC value (260.4%) were obtained from ogolcho, variety sprayed with Tilt 250 E.C. The highest yield (3.2 t ha-1) and maximum MRR (3700%) was obtained from ogolcho variety sprayed with Tilt 250 E.C. Similarly the highest net profit (67,780.00 ETB) was obtained from Ogolcho; variety sprayed with Tilt 250 E.C. Therefore, based our study, a combination of moderately resistant variety (ogolcho) with Tilt 250 E.C fungicide could be recommended or stem rust management in Meket district. However, the study was done on a single location and season. Thus, further location and season stratified study is needed to come up with holistic recommendation for the better management options of stem rust.