The aim of this study was to characterize and differentiate the Adwa, Arado, Medenes, and Begait cattle breeds in northern Ethiopia via univariate and multivariate analyses of phenotypic traits. Sixteen qualitative characteristics and nine morphometric traits were recorded for a total of 946 (604 females and 342 males) purposively selected adult cattle. The frequency, general linear model (GLM), and canonical discriminant (CANDISC) analysis procedures of the Statistical Analysis Software (SAS 9.0) were used to analyze the data. Qualitatively, Medenes and Begait, cattle breeds from lowland agroecology and livestock-based production systems, possess a convex facial profile, relatively larger dewlap, naval flap, and perpetual sheath, as well as more uniform and lighter body colors than the Adwa and Arado cattle breeds, which are from the midland agroecology and mixed crop–livestock production systems. Morphometrically, clear differences were observed among all of the studied cattle breeds, where the Begait, Medenes, Arado, and Adwa cattle breeds were ordered in descending order according to their overall body size. Moreover, multivariate analysis revealed significant differences among the breeds where each breed was placed under a separate group. However, such phenotypic distinctions among the four cattle breeds do not necessarily indicate genetic dissimilarities. Therefore, further inclusive genetic characterization studies involving the use of representative samples from the Adwa and Medenes cattle breeds are recommended to quantify the degree of genetic relationships among these breeds. Moreover, owing to the unknown breed-level population size, urgent conservation programs as well as genetic improvement strategies are needed to ensure sustainable utilization.