Lathyrism is an incurable neurological disorder, resulting from excessive consumption of grass pea (Lathyrus sativus), which clinically manifests as paralysis of lower limbs. Because of the high production of grass peas, a large number of people are expected to be affected by the disease in Northeast Ethiopia. However, there is no comprehensive study that quantified the magnitude of the problem. Therefore, in this study, we determined the prevalence of lathyrism and socioeconomic disparities in Northeast Ethiopia. A community-based cross-sectional study was used which used a quantitative method of data collection from January to February 2019. Data were collected from a total of 2,307 inhabitants in the study area using structured questionnaires. Lathyrism cases were identified using a case definition of symmetrical spastic leg weakness, and subacute or insidious onset, with no sensory deficit, and with a history of grass pea consumption before and at the onset of paralysis. The majority (56.8%) of participants were male, and 34.7% were aged 45 years or older. Overall, the prevalence of lathyrism was 5.5%, and it was higher in males (7.9%) than in females (2.5%). Moreover, the prevalence was higher among farmers (7.0%), very poor economic status (7.2%), those who produce grass pea (9.6%), and those who use clay pottery for cooking (6.2%) than their counterparts. The prevalence of lathyrism in Northeast Ethiopia is remarkably high. Therefore, we recommend lathyrism to be among the list of reportable health problems and incorporated in the national routine surveillance system.