Lean focuses on reducing waste and improving flow through methods like 5S, visual controls, Kanban, just-in-time production, and leveled production. Six Sigma uses statistical analysis and a defined methodology involving define, measure, analyze, improve, and control to reduce defects and variation. While both aim to improve quality, efficiency and customer satisfaction, Lean emphasizes eliminating waste and flow while Six Sigma's focus is on variation reduction and management through data-driven methods.