The rise of the southern textile industry in the early 1900s shifted the center of American textile production from the northeast to the Piedmont and created a new class of southern industrial workers: the “cotton mill people.” Throughout the 20th century, larger economic and political forces changed the industry and its people. Technological innovations, wars, and the diversification of the southern economy affected how textiles were made, the consumer demand for them, and mill workers’ wages and working conditions. The labor, civil rights, and women’s movements produced federal laws and legal victories that desegregated the mills, drew attention to the particular vulnerabilities of women workers, and provided protections for all workers against exploitation and poverty. Continuity, however, was as significant as change for mill workers. Women’s labor was always crucial in the mills, and women were key leaders in strikes and organizing drives. Unionization efforts were consistently undermined by technological innovations that replaced human labor, the global movement of capital, and the united power of mill owners and political leaders. Throughout the 20th century, cotton mill people struggled to resist the dehumanizing aspects of industrialization and insist on the dignity and value of their labor. The story of their struggles reveals important dimensions of 20th-century southern labor and life. With the movement of textile manufacturing from the American South to the Global South, their 20th-century struggles offer insights into the 21st-century struggles of textile workers worldwide.