The birth of a child all over the world often comes with joy. Birthweight is a strong predictor of an individual baby’s survival and a person’s personality. It is one of the key indicators of the health and viability of the newborn infant. It is desired that birthweight should be in the range of 2.5 kg to 4.0 kg. Low birthweight has been defined by the World Health Organization (WHO) as weight at birth less than 2.5 kg. This study seeks to evaluate some of the factors that affect birthweight in the Upper East Region of Ghana. One hundred mothers with singleton live births were sampled and interviewed at birth maternity blocks of Bolgatanga Regional Hospital, Bolgatanga and War Memorial hospital, Navrongo. The factors considered include: gestational age, gestational weight gain, maternal educational level, parity, cigarette smoking habits, type of fuel used for cooking, maternal drinking habits, type of physical exercise undertaken, period of rest during pregnancy, and fundal height. The average birthweight of infants born in the Upper East Region was 2.98±0.53 kg. Correlating the variables, it was observed that most of the above-mentioned factors correlated linearly but insignificantly (p > 0.05) with birthweight. Results of multiple regressions conducted established that maternal educational level significantly determines birthweight (ß = 0.34, p = 0.001). Within the limits of this research, maternal educational level contributed significantly in predicting birthweight in the region followed by duration of rest during pregnancy, pre-pregnancy weight, income level, and type of fuel used for cooking. The type of fuel used for cooking in the region contributed to low birthweight infants (ß = -0.06, p = 0.567). The estimated weight gain during pregnancy and healthy lifestyle recorded in this study could be responsible for the attainment of appropriate birthweight specified by WHO. It is recommended that education of the girl-child should be taken seriously in the region.