BackgroundGastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. However, there are limited studies on the latest survival trends and the impact of racial disparities on GIST patients' outcomes.MethodsWe obtained 12,808 GIST patients between 2001 and 2020 from the Surveillance, Epidemiology, and End Results (SEER) database in 17 original sites. Analysis utilizing the Kaplan-Meier method explored survival disparities and Cox regression was employed to assess the impact of prognostic factors.ResultsOur study revealed an increase in the GIST incidence per 100,000 people over the past two decades, along with a rise in relative survival rate (RSR). Age, gender, social groups, tumor site, size, stage, socioeconomic status, marital status, surgery, and systemic therapy are prognostic factors. Subgroup analysis indicated higher incidence and poorer survival trends among Non-Hispanic Blacks (NHB) (Incidence, 1.88 per 100,000 people; 120 Mo RSR, 61.6%, 2001 to 2020). Colonic GIST has the worst prognosis among different locations, while rectal and anal GIST has the best. Within these groups, Non-Hispanic White (NHW) with colonic GIST have the poorest prognosis (HR, 2.032; 95% CI, 1.476-2.798), whereas NHB with rectal and anal GIST have the best prognosis.ConclusionThe incidence and RSR of GIST both increased during 2001-2020. NHW with colonic GIST showed poorer survival, while NHB with rectal and anal GIST revealed better survival, highlighting the importance of targeted clinical management for GIST.