Neuroimaging is a valuable diagnostic tool for the early detection of neonatal brain injury, but equipment and radiologic staff are expensive and unavailable to most hospitals in developing countries. We evaluated an affordable, portable ultrasound machine as a quantitative and qualitative diagnostic tool and to establish whether a novice sonographer could effectively operate the equipment and obtain clinically important information. Cranial ultrasonography was performed on term healthy, pre-term and term asphyxiated neonates in Rwandan and Kenyan hospitals. To evaluate the detection of ventriculomegaly and compression injuries, we measured the size of the lateral ventricles and corpus callosum. The images were also assessed for the presence of other cerebral abnormalities. Measurements were reliable across images, and cases of clinically relevant ventriculomegaly were detected. A novice sonographer had good-to-excellent agreement with an expert. This study demonstrates that affordable equipment and cranial ultrasound protocols can be used in low-resource settings to assess the newborn brain.