Background: Oropharyngeal carcinomas are characterized by an increasing incidence and a relatively good prognosis. Nonetheless, a considerable number of patients develops metachronous distant metastases; identification of these patients is an urgent medical need. Methods: This is a retrospective multicenter evaluation of 431 patients. All patients underwent [¹⁸F]-FDG positron emission tomography (PET). The cohort was split into an explorative group (n = 366) and a validation group (n = 65). Lesions were manually delineated in the explorative group and automatically delineated by a convolutional neuronal network (CNN) in the validation group. Quantitative PET parameters standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated for primary tumors (_prim) and tumor plus lymphnodes (_all). Association of parameters with freedom from distant metastases (FFDM) and overall survival (OS) was tested by cox regression analyses. Results: In the explorative group, univariate analyses revealed an association of metric MTV_prim (p = 0.022), MTV_all (p < 0.001) and TLG_all (p < 0.001) with FFDM, binarized parameters were also associated with FFDM (p < 0.001 and p = 0.002). Bootstrap analyses revealed a significantly better association of TLG_all compared to TLG_prim with FFDM (p = 0.02). MTV_all and TLG_all remained significantly associated with FFDM upon multivariate testing (p = 0.002, p = 0.031, respectively). In the validation group, the cutoff value for TLG_all but not for TLG_prim was significantly associated with FFDM (HR = 3.1, p = 0.045). Additional analyses with manually delineated contours of the validation cohort revealed a similar effect (HR = 3.47, p = 0.026). No considerable differences between HPV positive and negative disease were observed. Conclusions: TLG_all is a promising biomarker to select OPC patients with high risk for metachronous distant metastases.