Manual handling of heavy grain bags is a commonplace activity across agriculture produce supply chain. In the present research, a manual material handling involving lifting, lowering, and carrying grain bags along the paths of variable characteristics is critically analyzed to explore the risk associated with it. The humans engaged in this activity are found to be facing discomfort, suffering from pain and musculoskeletal disorders, and undergoing medication for the same. This study proposes and demonstrates a structured ergonomic evaluation methodology to not only assess the level of discomfort/pain but also evaluate risk factors such as load handled, method of handling, frequency of handling, awkward postures, path characteristics, and so on. It employs a systematic multimethod approach consisting of Nordic Musculoskeletal Questionnaire and Borg Rating of Perceived Exertion, Ovako Working posture Assessment System, NIOSH Lifting Equation, Rapid Entire Body Assessment, and Key Indicator Method. The study reveals that about 94% of the sample population suffered from moderate to severe discomfort in ankle, knee, and lower back. Eight basic activities responsible for risky postures are identified. Frequency of handling, weight being handled, back bending/twisting, poor coupling, and walking surface are observed as major contributors to musculoskeletal discomfort. Carrying on shoulder is found to be riskier than carrying on back; however, the risk is found to be significantly lowered by carrying on backpack. The present study identifies the need for task redesign, proper gripping arrangements, auxiliary devices for lifting/carrying, and improvement in the path characteristics.