Introduction: Stroke is a leading cause of disability and mortality worldwide, with significant public health consequences. In clinical practice, prognosis relies on clinical, neuroimaging, and laboratory parameters, none of which are sufficiently sensitive or specific to enable early prognosis and facilitate treatment decisions. The pathophysiology of ischemic stroke (IS) increasingly recognizes neuroinflammation as a key factor, and biomarkers like suppression of tumorigenicity 2 (ST2) are emerging as important indicators of inflammatory responses that may influence the progression of neuronal damage and overall patient outcomes. Aim: This study aimed to determine whether the dynamics of the release of the inflammatory serological biomarker ST2 could predict IS outcome, alongside of assessing the usefulness of clinical, neuroimaging, and routine laboratory parameters in predicting IS outcomes. Methods: A prospective, longitudinal, observational study was conducted involving patients with acute IS. ST2 concentrations and clinical, neuroimaging, and routine laboratory parameters were measured at seven time points, starting at admission (T0), followed by consecutive 24-hour intervals (T1−T6). After 90 days from the onset of IS, functional outcomes were assessed using the modified Rankin Scale (0−2 for good outcome and 3−6 for poor outcome), along with all-cause mortality. Results: The study included a total of 20 IS patients. After 90 days, 15 patients had poor outcomes, and eight patients died. The analysis of ST2 release dynamics showed the highest concentration at T1, followed by a gradual decline. Significant differences in ST2 concentrations between the groups with good and poor outcomes and between survivors and deceased were found in most measurement points, with the highest prognostic accuracy at T1 (median 38 hours) at a cutoff value of >18.9 μg/L. Additionally, statistically significant differences between the same groups were observed in National Institutes of Health Stroke Scale (NIHSS), C-reactive protein (CRP) and albumin concentrations, prognostic nutritional index (PNI), platelet counts, and infarct volume (IV). Conclusion: The study's findings confirmed the importance of ST2 dynamics in the outcome of IS, opening avenues for exploring its clinical application, particularly in the early stages of IS, where ST2 as a biomarker could significantly enhance patient care. Among clinical parameters, NIHSS, IV and, to a lesser extent, PNI proved effective for outcome prediction. At the same time, routine laboratory tests, except for CRP, did not show usefulness in monitoring dynamics or predicting outcomes.