The Eastern Cape Province of South Africa has climatic conditions which differ from region to region. The groundnut (Arachis hypogaea L.) cultivars, as it is the case with other crops, do not always perform equally well in the varying conditions. Abiotic stresses such as drought, extreme temperatures, and high soil acidity restrict plant growth. Lack of studies on adaptability of commercial groundnut cultivars in the Eastern Cape necessitated this study. Abiotic and biotic factors are not the only limiting factors: calcium availability in the soil is also a limiting factor in groundnut production. The aim of the study was to identify best suited cultivars for climatic conditions of Mthatha and Lusikisiki regions of the Eastern Cape. Two similar field experiments were conducted in the two locations with different climatic conditions. The results showed significant differences (P<0.05) in genotypes with respect to seed yield in both locations. Kwarts produced higher seed yield of 1155 kg ha-1 in Mthatha, while the same genotype produced low seed yield of 630 kg ha-1 in Lusikisiki location. In Lusikisiki the highest seed yield was recorded in Anel (936 kg ha-1) which produced low yield of 692 kg ha-1 in Mthatha. The genotypes that performed well in Mthatha in 2010/11 season included Kwarts, Nyanda, ICGV-SM 95714 and Mwenje. These genotypes were further used to investigate their response to calcium supplementation at flowering stage under conditions of Mthatha in the 2011/12 season. The results were significantly different for calcium absorption (P<0.05). Nyanda, Kwarts and Mwenje responded positively to calcium application at flowering stage producing relatively high yield of 153, 150 and 110 kg ha-1, respectively. Oil content was significantly increased by calcium application at flowering in Nyanda with 27.28% compared to 20.7% without Ca.