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The aim of this study was to assess crop residue biomass potential for second generation biofuel production in the Lawra–Nandom district of Ghana. The methods used in this study included interviews, survey, field and laboratory experiments. The findings show that total annual crop residues production in the Lawra–Nandom district amounts to about 272,000 tonnes. Among the major crops grown in the district, sorghum crop generates the largest quantity of residues, contributing 59 per cent by weight of the total residues. Ethanol production potential could reach 40 million litres if 40 per cent of the average residue generated between 2003 and 2012 were used for energy purposes. The net energy balance of the biofuel production process was 1718.7 MJ with a ratio of energy output to input being 1.31. Second generations biofuels are expensive compared to first generation and research efforts aimed at technology improvement and cost reduction must intensify in order to make the technology attractive to developing countries.