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The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5 cm×5 cm×5 cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter. Across the searched range of charges e/24-e/2 no excess of FCP candidate tracks is observed over background, setting leading limits on the underground FCP flux with charges e/24-e/5 at 90% confidence level. Using the low background environment and segmented geometry of CUORE, we establish the sensitivity of tonne-scale subkelvin detectors to diverse signatures of new physics.