The creation of Wilmington's Sister City Commission stems from the non-profit organization, Sister Cities International, which works to build relationships between cities in the United States and abroad. The organization's goal is to promote learning and cultural exchange between communities. The program began in 1956 under President Eisenhower as a part of the National League of Cities, however in 1967 Sister Cities International became a separate corporation due to its popularity.

In September of 1986, the Wilmington City Council formed Wilmington’s Sister City Commission as a local extension of Sister Cities International. The commission worked to formed the city's first relationships with Dandong, China in 1897 and Doncaster, England in 1989. Wilmington briefly ended its relationship with Dandong in 1989 due to the Tiananmen Square protests and massacre. The relationship was restored a few years later and continues to exist today. In 2004 and 2007 respectively, Bridgetown, Barbados and San Pedro, Belize were added to Wilmington’s list of sister city partnerships. Additionally, the Sister Cities Association was formed in Wilmington in 2004 as non-profit organization to facilitate these relationships with sister cities. Today, the Wilmington Sister City Commission, Sister Cities Association, and Sister Cities International maintain a three way partnership to carryout the mission of the program.