Schizophrenia-spectrum disorders (SSD) are highly heterogeneous in risk factors, symptom characteristics, and disease course outcome. Although speech anomalies have long been recognized as a core symptom of SSD, speech markers are an unexplored source of symptom heterogeneity that may be informative in recognizing relevant subtypes. This study investigated speech heterogeneity and its relation to clinical characteristics in a large sample of patients with SSD and healthy controls. Speech samples were obtained from 142 patients with SSD and 147 healthy controls by means of open-ended interviews. Speech was analyzed using standardized open-source acoustic speech software. Hierarchical clustering was conducted using acoustic speech markers. Symptom severity was rated with the Positive and Negative Syndrome Scale, and cognition was assessed with the Brief Assessment of Cognition for Schizophrenia. Three speech clusters could be distinguished in the patient group that differed regarding speech properties, independent of medication use. One cluster was characterized by mild speech disturbances, while two severely impaired clusters were recognized (fragmented speakers and prolonged pausers). Both clusters with severely impaired speech had more severe cognitive dysfunction than the mildly impaired speakers. Prolonged pausers specifically had difficulties with memory-related tasks. Prolonged pausing, as opposed to fragmented speaking, related to chronic active psychosis and refractory psychotic symptoms. Based on speech clustering, subtypes of patients emerged with distinct disease trajectories, symptomatology, and cognitive functioning. The identification of clinically relevant subgroups within SSD may help to characterize distinct profiles and benefit the tailoring of early intervention and improvement of long-term functional outcome. (PsycInfo Database Record (c) 2022 APA, all rights reserved).