This study presents a 3-D Fluid-Structure Interaction (FSI) simulation of breastfeeding mechanism to provide a better understanding of the milk flow behavior in the ductal system of the human breast as the breast interacts with the infant's oral cavity. The breast geometry consists of one lobe with three-bifurcation levels. The boundary conditions include: (1) The intraoral vacuum pressure, obtained from the clinical measurements, (2) Dynamic motion of the tongue, nipple, and jaw (maxilla and mandible) motion captured by ultrasound images. Simulation is conducted from the instance of latching and continues for two cycles of periodic tongue motion and in various boundary conditions and mouthing positions. The results from the simulation show that milk removal is not only due to the negative pressure applied by the infant sucking, but also the tongue movement and mouthing and squeezing of nipple and breast, i.e. a positive force deforming the nipple is responsible for the expression of milk. The developed model can contribute to a better understanding of breastfeeding complications due to physical infant and/or breast abnormalities and the design of medical devices such as artificial teats and breast pumps.