The barriers to and opportunities for adopting green manufacturing practices (GMP) have not been well investigated in Ethiopian manufacturing industries. The objectives of this study were to identify the potential barriers to and determinants of adopting GMP among medium- and large-scale manufacturing businesses in northern Ethiopia. To achieve the objectives, primary data were collected from 131 medium- and large-scale manufacturing companies through interviews. Exploratory factor analysis and multiple linear regression modelling were used to answer the research questions. Company specific characteristics: managers' experience, number of persons engaged, scale size of the company, age of the company, and whether the company has an environmental management department or not have significant influence on adoption of GMP. Lack of environmental knowledge, business environment related barrier, societal influence, technological barrier, financial barrier, organizational barrier, and regulatory or government barrier were the significant barriers to adoption of GMP. The significant industry-specific characteristics and the adoption barriers identified as determinants of GMP can help medium- and large-scale manufacturing enterprises to change their manufacturing practices to GMP. In addition, the findings of this study can be used to promote environmental sustainability in manufacturing.