Magnetic resonance Imaging is the gold standard for assessment of soft tissues; however, X-ray-based techniques are required for evaluating bone-related pathologies. This study evaluated the performance of synthetic computed tomography (sCT), a novel MRI-based bone visualization technique, compared with CT, for the scoring of knee osteoarthritis. sCT images were generated from the 3T T1-weighted gradient-echo MR images using a trained machine learning algorithm. Two readers scored the severity of osteoarthritis in tibiofemoral and patellofemoral joints according to OACT, which enables the evaluation of osteoarthritis, from its characteristics of joint space narrowing, osteophytes, cysts and sclerosis in CT (and sCT) images. Cohen's κ was used to assess the interreader agreement for each modality, and intermodality agreement of CT- and sCT-based scores for each reader. We also compared the confidence level of readers for grading CT and sCT images using confidence scores collected during grading. Inter-reader agreement for tibiofemoral and patellofemoral joints were almost-perfect for both modalities (κ = 0.83–0.88). The intermodality agreement of osteoarthritis scores between CT and sCT was substantial to almost-perfect for tibiofemoral (κ = 0.63 and 0.84 for the two readers) and patellofemoral joints (κ = 0.78 and 0.81 for the two readers). The analysis of diagnosis confidence scores showed comparable visual quality of the two modalities, where both are showing acceptable confidence levels for scoring OA. In conclusion, in this single-center study, sCT and CT were comparable for the scoring of knee OA.