Abstract: Background and Objective: Two field experiments (2018 and 2019) were conducted at the research field of the University of Education, Winneba, Mampong, Ashanti campus from May to August to determine the influence of row spacing and NPK fertilizer on growth and yield of groundnut under rain-fed condition in transitional zone of Ghana. Materials and Methods: The experimental design was a 2×3×2 factorial laid in a randomized complete block design with 3 replications. The factors studied included: (A) Variety [(i) Yenyawoso and (ii) Adepa], (B) Row spacing [(i) 30×15 cm, (ii) 40×15 cm, (iii) 50×15 cm] and (C) Fertilizer rates [ (i) 20 kg ha–1 NPK 15-15-15 and (ii) No fertilizer (control)]. Results: The result according to the two year cropping seasons showed that Yenyawoso groundnut was found promising to produce high vegetative biomass and Adepa groundnut for high yield and heavy seeds. The 30×15 and 50×15 cm spacing produced heaviest pod weight and high yield respectively. Interaction effect between variety×spacing and variety×spacing×fertilizer was significant with number of branches, yield and haulm weight at harvest. Conclusion: Farmers are encouraged to grow Yenyawoso and Adepa groundnut varieties using 30×15 and 50×15 cm spacing for taller plants, highest number of branches, wider canopy spread and high yield and quality seeds with regard to weight respectively as well as apply NPK 15-15-15 at 20 kg ha–1 at the initial growth stage to boost groundnut growth and development.