Office and Professional Employees International Union, Southern Region records

Clerical unions began forming in the early 1900s. By 1920, the American Federation of Labor (AFL) had issued charters to more than 50 clerical unions. In 1942, the locals banded together to form the International Council of Office Employee Unions. In 1945, this union received a charter from the AFL as the Office Employees International Union. At the time of its founding, the union had about 22,000 members. In 1946 and again in 1948, the union conducted major strikes in New York City that led to the organization thousands of workers on Wall Street. At roughly the same time, the union began organizing locals in Vancouver, British Columbia and Montreal, Quebec. By 1960, the union had doubled in size to nearly 50,000 members.

In 1965, the union adopted its current name. In the 1990s, OPEIU began major organizing drives in the insurance industry, organizing several thousand workers at CUNA Mutual and Prudential. A similar organizing drive at Allstate ended after the National Labor Relations Board ruled that the 10,000 workers were independent contractors. OPEIU also began organizing in the health care industry, organizing office workers at a number of health insurers. But it also began organizing registered nurses and other health care workers in limited numbers around the United States. In 1998, the much-raided collective bargaining arm of the Pennsylvania Nurses Association affiliated with OPEIU, adding 2,500 nurses to the union's rolls. By 2005, OPEIU represented about 5,000 RNs, making it the sixth largest nurses' union in the AFL-CIO.