Using a comparative mixed methods approach involving two districts each in Southern and Northern Ghana, this article addresses the question: under what conditions, and at what scale does smallholder agricultural commercialisation promote or hinder food security? Specifically, it presents an analysis of how gender and spatial inequalities in resource control determine differential capacities to commercialise and the implications of agricultural commercialisation for food security in an export commodity dominated Southern Ghana versus a food crop dominated Northern Ghana. We found gender gaps in commercialisation capacity that did not seem to disappear even in the presence of land abundance because the gaps are structural. We also found that, in some contexts, high rates of commercialisation do not mean accumulation. Among females in parts of Northern Ghana, apparent high commercialisation rates are driven by necessity, and thus constitutes ‘distress push commercialisation’, which has negative food security implications. While we found no evidence of an overall positive association between commercialisation and food security, we show that in the export crop dominated high commercialisation zone of Southern Ghana, commercialisation enhances food security only up to a threshold above which further resource allocation towards non-food cash crops hurts food security because of inefficient food markets.