Ultrasound-assisted extraction (UAE) methods for food analysis are recognized as being in accordance with the principles of green analytical chemistry (GAC). Reference standard methods generally use microwave-assisted extraction (MAE) for sample digestion; however, the use of ultrasonication processes has many advantages. Herein, a simple, and economical method for the determination of Cd and Pb in fruits and vegetables for food safety monitoring is reported. This method was optimized using a standard reference material (SRM, spinach leaves) through a multivariate experimental design (optimal conditions: 0.5 g of sample, 15 min of sonication, and 20.00 mL of 2.5 mol L−1 HNO3) and subsequently validated. The limits of detection obtained were one or two orders of magnitude lower than those achieved with MAE, making this a promising technique for contaminants monitoring. The UAE method was then tested on vegetable samples (apples, carrots, tomatoes, and lettuce) obtained from commercial sources in Uruguay and a comparison was made with samples treated by MAE. Both processes yielded comparable results, and the levels of Cd and Pb in all samples were below the maximum allowed concentration (MAC) established by the World Health Organization (WHO). In addition, to provide insight into the mechanism by which the ultrasonic process aids extraction, confocal optical images of the surface of the SRM were obtained. The leaves were examined after treatment at different sonication times (5?20 min). The confocal microscopy images show the effects of the ultrasonic treatment on the plant tissue, including desaturation, erosion, and abrasion, which increased with increasing sonication time. In conclusion, the UAE method meets and overcome the requirements of a standard method for food safety assurance.