Background: In principle, trade and investment agreements are meant to boost economic growth. However, the removal of trade barriers and the provision of investment incentives to attract foreign direct investments may facilitate increased trade in and/or more efficient production of commodities considered harmful to health such as tobacco. We analyze existing evidence on trade and investment liberalization and its relationship to tobacco trade in Sub-Saharan African countries. Methods: We compare tobacco trading patterns to foreign direct investments made by tobacco companies. We estimate and compare changes in the Konjunkturforschungsstelle (KOF) Economic Globalization measure, relative price measure and cigarette prices. Results: Preferential regional trade agreements appear to have encouraged the consolidation of cigarette production, which has shaped trading patterns of tobacco leaf. Since 2002, British American Tobacco has invested in tobacco manufacturing facilities in Nigeria, Kenya and South Africa strategically located to serve different regions in Africa. Following this, British America Tobacco closed factories in Ghana, Rwanda, Uganda, Mauritius and Angola. At the same time, Malawi and Tanzania exported a large percentage of tobacco leaf to European countries. After 2010, there was an increase in tobacco exports from Malawi and Zambia to China, which may be a result of preferential trade agreements the EU and China have with these countries. Economic liberalization has been accompanied by greater cigarette affordability for the countries included in our analysis. However, only excise taxes and income have an effect on cigarette prices within the region. Conclusions: These results suggest that the changing economic structures of international trade and investment are likely heightening the efficiency and effectiveness of the tobacco industry. As tobacco control advocates consider supply-side tobacco control interventions, they must consider carefully the effects of these economic agreements and whether there are ways to mitigate them.