The global increase in obesity has occurred in parallel to a dietary shift from traditional staple foods to ultra-processed foods (UPF), spurring scientific interest in UPF as a driver of the obesity pandemic. Herein, we summarize the current evidence regarding the role of UPF in obesity, with a specific focus on potential biological mechanisms. The literature strongly supports and corroborates ecological, epidemiological and mechanistic lines of research indicating that dietary patterns high in UPF promote overeating and increase the risk of overweight and obesity. Experimental evidence demonstrates that the soft texture, high energy density and hyperpalatable nutrient combinations of UPF facilitate excessive energy intakes by affecting ingestive behaviours, satiety signalling and food reward systems. Although not fully elucidated, it is plausible that several other UPF attributes (such as emulsifiers, non-nutritive sweeteners, acellular nutrients, and contaminants from processing and packaging materials) contribute to their obesogenic effects through a myriad of physiological pathways, including altered absorption kinetics, glycaemic response and the gut microbiota composition and function. To stem the global rise in obesity, multipronged policy efforts are needed to reduce UPF consumption and create health-promoting food systems.