Homeostatic imbalance of essential trace elements is deeply involved in many pathophysiological states, especially in joint disorders such as gout. A total of 64 elements were measured in the serum samples in three regionally independent groups of patients with gouty arthritis (n = 100) and an age-matched healthy control group (n = 40) by inductively coupled plasma-mass spectrometry (ICP-MS). A distinct elemental profile of gouty arthritis encompassing significantly altered Li, Al, Ti, Fe, Cu, Se, Sr, Ta, Hg, Bi, Th, and U was obtained with a sensitivity of 0.97 (95% confidence interval (CI): 0.92–0.99) and a specificity of 0.95 (95% CI: 0.83–0.99) for gout diagnosis. An independent group of 52 subjects (39 gout patients and 13 healthy controls) was further used to validate the elemental signature, yielding a sensitivity of 1.00 (95% CI: 0.91–1.00) and a specificity of 1.00 (95% CI: 0.75–1.00) for gout prediction. It is also noteworthy that we were able to achieve ≥95.7% correct classification rate in both discovery and validation groups using only three elemental markers, Li, Al, and U. We also observed a good correlation between Li, Zn, and Cu and the other two risk factors, age and serum urate concentration, in gout patients. Our findings underscore that gouty arthritis possesses a unique elemental expression profile regardless of many other nutritional and environmental factors.