The departure will take effect from January 1 and the Guangzhou-based airline "will explore the possibilities to establish new partnerships with advanced airlines around the world," China Southern said in a statement.
China Southern joined the SkyTeam alliance in November 2007 as the first airline from continental China.
Analysts noted that American Airlines -- which belongs to the rival Oneworld alliance -- had become more closely linked to China Southern, in which it took a 2.68 percent stake in 2017 for $200 million.
The tie-up will allow American to tap into the Chinese market, while boosting China Southern's ambitions of raising its global profile.
China is now the world's second-largest aviation market, and increasing demand for air travel among its booming middle class is expected to ultimately push it past the United States.
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