The Japan Sea in the western North Pacific was connected to the deep Pacific via deep seaways before it became a semi-closed marginal sea. However, the timing of the semi-closure and its cause(s) remain debatable. To further constrain the timing, for the first time we analyzed Nd isotopic compositions of fossil fish teeth and fish debris deposited in the Japan Sea (Integrated Ocean Drilling Program [IODP] Site U1425, ∼2000 m water depth) over the past 10 m.y. Neodymium isotope values (–4.5 to –3.2 εNd) in the Japan Sea prior to 4.5 Ma illustrate that the deep Japan Sea was composed of an admixture of less-radiogenic Lower Circumpolar Deep Water (avg. –4.3 εNd) and more-radiogenic North Pacific Deep Water (avg. –2.2 εNd), potentially with inflow from the Okhotsk Sea. At 4.5 Ma, εNd values fell to –5.5 εNd within a span of 140 k.y., suggesting that the deep-water communication between the Japan Sea and the North Pacific rapidly declined. We argue that active mountain building in the northern Japan arc, initiated by accelerated Pacific plate motion from the late Miocene to mid-Pliocene, caused the shallowing/narrowing of the Japan Sea–Pacific seaways and rapidly made the Japan Sea semi-closed at 4.5 Ma. As a result, the Japan Sea circulation patterns were realigned; a cyclonic circulation was developed and drew less-radiogenic Amur River–influenced Okhotsk Sea water into the Japan Sea.