Purpose This prospective study aimed to compare the diagnostic performance of [ 18 ]FDG PET/MRI and PET/CT for the detection of distant metastases and distant second primary cancers in patients with head and neck squamous cell carcinoma (HNSCC). Methods A total of 103 [ 18 F]FDG PET/MRI examinations immediately followed by PET/CT were obtained in 82 consecutive patients for staging of primary HNSCC ( n = 38), suspected loco-regional recurrence/follow-up ( n = 41) or unknown primary HNSCC ( n = 3). Histology and follow-up > 2 years formed the standard of reference. Blinded readers evaluated the anonymized PET/MRI and PET/CT examinations separately using a 5-point Likert score. Statistical analysis included: receiver operating characteristic (ROC) analysis, jackknife alternative free-response ROC (JAFROC) and region-of-interest (ROI)-based ROC to account for data clustering and sensitivity/specificity/accuracy comparisons for a score ≥ 3. Results Distant metastases and distant second primary cancers were present in 23/103 (22%) examinations in 16/82 (19.5%) patients, and they were more common in the post-treatment group (11/41, 27%) than in the primary HNSCC group (3/38, 8%), p = 0.039. The area under the curve (AUC) per patient/examination/lesion was 0.947 [0.927–1]/0.965 [0.917–1]/0.957 [0.928–0.987] for PET/MRI and 0.975 [0.950–1]/0.968 [0.920–1]/0.944 [0.910–0.979] for PET/CT, respectively ( p > 0.05). The diagnostic performance of PET/MRI and PET/CT was similar according to JAFROC ( p = 0.919) and ROI-based ROC analysis ( p = 0.574). Sensitivity/specificity/accuracy for PET/MRI and PET/CT for a score ≥ 3 was 94%/88%/89% and 94%/91%/91% per patient, 96%/90%/91% and 96%/93%/93% per examination and 95%/85%/90% and 90%/86%/88% per lesion, respectively, p > 0.05. Conclusions In HNSCC patients, PET/MRI and PET/CT had a high and similar diagnostic performance for detecting distant metastases and distant second primary cancers.