The Office and Professional Employees International Union (OPEIU) began as a "union's union." In 1904 the American Federation of Labor (AFL) started granting affiliated charters to clerical workers in the offices of trade unions and began referring to the new unions as "federal labor unions." The organization of clerical workers in trade union offices was quite sucessful. The workers were eager to organize, and the officials of the unions usually offered no resistance.

Despite setbacks in the 1920s, federal labor union activists continued their organizing efforts and expanded into offices in service industries and private businesses in the 1930s. In July 1942 men and women representating the federal labor unions gathered in Chicago and formed the International Council of Office Employes. Three years later the AFL replaced the affiliated charters with an international charter, created the Office and Professional Employees International Union, and broadened the focus of the union. It specifically charged the new international union to organize clerical workers in all offices in the United States and Canada, not just those of trade unions. Organizing office workers in businesses, however, was much more difficult than organizing employees of trade unions. Michael Troutman and Amy Blumenshine note a number of problems confronting unions attempting to organize clerical workers:

Although the reality may be different, significant numbers of clerical workers continue to perceive themselves as temporary members of the clerical workforce. Clericals fear job loss which employers may threaten for pro-union activity. Some clericals develop strong loyalties to their bosses due to office configuration and psychological needs. Clericals have little contact with or understanding about unionization and tend not to associate unions with their own needs as white-collar workers. Clerical attitudes toward unions are often marked by suspicion and misconception due to distortions caused by the media and managerial communications.

The OPEIU faced all of these problems. Not surprisingly many of the Union's early successes were in industries that had other unionized employees. For example, in the 1940s and earlier the OPEIU was particularly active in the offices of shipbuilders, most notably in Oakland, Portland, Vancouver, Tampa, and New York City.

After initial efforts in unionized industries, the OPEIU looked toward the largely unorganized industries of banking and insurance. In the 1960s and 1970s the OPEIU leaders organized many banking offices and grew accordingly. The offices of the National Bank of Washington, Washington, D.C. brought 565 new members to the Union. Not all of the Union's efforts in the banking industry have been successful. Recently Local 29 in Oakland, responding to a request for unionization by employees of the Barclays Bankcard Center in Concord California, attempted to organize the Center but lost a NLRB election on 10 July 1986. The OPEIU has been even more active in the insurance industry than in banking. Some of the OPEIU's largest increases in membership have been in offices of insurance companies; for example, the offices of Kaiser-Permanente, Oakland, CA, and Cleveland, OH and Group Health Cooperative of Puget Sound, Seattle, WA each brought more than 1,000 new members to the Union.

In many ways the development of OPEIU Local 3 in San Francisco mirrors the history of the OPEIU international. In 1911 Samuel Gompers of the American Federation of Labor chartered the Stenographers, Typewriters, Bookkeepers, and Assistants Association No. 13188, the predecessor of Local 3. The Association had only 100 members, most of whom were men holding positions in the offices of trade unions or in the offices of the city government of San Francisco. The Association was reorganized in 1937, granted a new charter, and renamed OPEIU Local 36, but by 1955, when the Union became Local 3, it had only 100 remaining members. The fortunes of the Union were turned by Phyllis K. Mitchell, who began serving as recording secretary in 1943 and then served as president for twenty-five years. By 1965 she had increased the Union's membership eleven fold. She secured agreements in public and private offices in industries from media to shipping to baking.

One of greatest successes of Local 3 in San Francisco was in the insurance industry. In 1972 Local 3 won a NLRB election at Blue Shield of California. The membership of the Local, which had been 1,100 in 1965, jumped to nearly 3,000. Not only did the membership increase, but its composition changed too. The workforce at Blue Shield was comprised primarily of women office workers, especially Filipinas. After winning the election Local 3 broke the Company's freeze on wages and increased them by one third.

Local 3 continued to represent employees at Blue Shield through the mid-1980s. It survived an open shop vote in 1981, but in 1987, after Blue Shield reorganized and decentralized its workforce, the remaining 350 employees represented by the Union voted to decertify it. The decertification of Local 3 at Blue Shield followed decertification of an OPEIU local at Blue Shield of St. Louis in 1982. Despite these losses, OPEIU still represents nearly one-half of the unionized Blue Shield employees across the nation in 1987 and is one of the largest unions in the country.