Small- and medium-sized enterprises (SMEs) are the driving force behind a large number of innovations and contribute to the growth of the national economy through employment creation, investments and exports. For manufacturing SMEs in countries like India, the production worker is one of the key elements in the conversion process of inputs to outputs. Therefore, it becomes imperative for such SMEs to focus on the production issue, namely, the importance of the role of production workers for turning out an output of near Six Sigma quality level for Six Sigma approach has been accepted as the standard for world class manufacturing. As a step towards achieving this level of output quality, production-worker related problems that afflict the growth and success of manufacturing SMEs, especially, in the North Karnataka, must be resolved. This paper focuses on developing a holistic approach for enhancing the output level of a manufacturing SME towards Six Sigma level by way of improving the overall effectiveness of production worker. This approach can help manufacturing SMEs across the nation to implement strategies like Six Sigma from the root level.