Potato is one of the most widely grown vegetable crops in Ethiopia in general and in Koga Irrigation Scheme of North Mecha District, Amhara Region in particular. Plant spacing and seed tuber sizes are important agronomic management in the production of potato. However, farmers did not use the optimum size of seed tuber with required spacing, which contributes to low yield. Afield experiment which was aims to evaluating the effect of seed tuber size and intra row spacing on growth and tuber yield of potato at Kudmi kebele of Koga Irrigation Scheme was conducted during the irrigation season of 2020/2021. The treatments consisted of four levels of seed tuber sizes in gram (25-50, 50-75, 75-100, 100-125) combined with three levels of intra row spacing in centimeter (20, 30, and 40) which were laid down in randomized complete block design with 4x3 factorial arrangement with three replications. Growth and yield related parameters were collected and analyzed using SAS 9.4 software. The result indicated that day to 50% flowering, days to 90% maturity, plant height, average tuber weight, tuber number per hill, total tuber yield, average tuber yield per hill, large and medium-sized tuber yields were affected by the main factors of seed tuber size and intra-row spacing. Significant interaction effects were observed on parameters such as stem number per plant, marketable tuber yield, unmarketable tuber yield, very small-sized and small-sized yields. The highest marketable tuber yield (28.98 t/ha) was recorded from 75-100g seed tuber size with 40cm intra row spacing. The marketable tuber yield was positively correlated with main stem number, plant height, average tuber weight, medium-sized, large-sized and total tuber yields whereas negatively correlated with very small-sized tuber and unmarketable tuber yield. Based on the partial budget analysis large tuber size (75-100g) with (40cm) intra row spacing resulted in the maximum net benefit (219734.7Eth-Birr/ha) with an acceptable level marginal rate of return (274.13%), whereas the lowest net benefits (115002Eth-Birr/ha) was obtained from the interaction effect of (25-50g) with (20cm). So that large size seed tubers could be recommended for economical and agronomical feasible production of potato. However, the study was limited to one season, location and single variety of high plant vigor. Therefore, further study over season and location is required to make viable recommendation.