There is an urgent need for agri-food system transformation to achieve global sustainability goals. Innovations can play a key role in this transformation but often come with both sustainability synergies and trade-offs. One such innovation is agricultural mechanization, which is spreading rapidly in parts of the Global South and is high on the policy agenda in others. The rapid spread of mechanization is fundamentally changing the character of agri-food systems in the Global South, with both positive and negative effects. However, while some of these effects have been well explored, no study so far has systematically reviewed the sustainability synergies and trade-offs associated with mechanization, undermining necessary accompanying research and policy efforts. This review provides an overview of the progress toward mechanization across the Global South, identifies drivers and barriers, assesses sustainability synergies and trade-offs, and discusses options to maximize sustainability outcomes. The review is the first to holistically assess the potentials and risks of agricultural mechanization for the sustainable transformation of agri-food systems in the Global South, taking into account all pillars of sustainability. The review suggests that agricultural mechanization is needed to make agri-food systems more sustainable concerning various economic and social aspects, such as labor productivity, poverty reduction, food security, and health and well-being. However, there are also sustainability risks concerning environmental aspects such as biodiversity loss and land degradation, and economic and social concerns related to lacking inclusiveness and growing inequalities, among others. A wide range of technological and institutional solutions is identified to harness the potential of agricultural mechanization for sustainable agri-food system transformation, while at the same time minimizing the risks. However, more efforts are needed to implement such solutions at scale and ensure that mechanization contributes to agri-food systems that respect all pillars of sustainability.