The benchmark Nikkei share average <.N225> closed 1.78% higher at 25,349.60, marking its highest closing level since June 1991.
The index also extended gains to a seventh consecutive session, its longest rally since October 2019.
The broader Topix gained 1.66% to 1,723.65, its highest level since Feb. 7. All but three of the 33 sector sub-indexes on the Tokyo exchange traded higher.
Along with optimism after U.S. drugmaker Pfizer said on Monday that its initial trial results showed that the experimental COVID-19 vaccine is more than 90% effective, Japanese shares were supported by upbeat company earnings reports and receding U.S. political uncertainty, analysts said.
U.S. stock futures edged higher in Asian trade, while upbeat company earnings also provided a tailwind to the market.
Cyclical financials sectors outperformed as they benefited from an overnight jump in U.S. Treasury yields, with insurers <.IINSU.T> and banks <.IBNKS.T> up 3.06% and 2.72%, respectively.
Meanwhile, airlines ANA Holdings and Japan Airlines, which had soared around 17% each on Tuesday on the vaccine rally, lost steam and were last down 1.13% and 2.11%, respectively. Internet service provider DeNA was among the largest percentage gainers in the index, soaring more than 12% after it posted upbeat half-year earnings.
Regional banks gained after the Bank of Japan unveiled on Tuesday a scheme aimed at incentivising regional lenders to consolidate and help revitalise regional economies.
Concordia Financial Group jumped more than 4.7%, followed by Shimane Bank and Chiba Bank rising 5.61% and 3.57%, respectively.
Kansai Mirai Financial Group jumped 13.4% after Resona Holdings said it would pay up to 66.15 billion yen ($628.38 million) to take full control of the company. Resona Holdings climbed nearly 4.47%.
($1 = 105.2700 yen)
(Reporting by Eimi Yamamitsu; Editing by Rashmi Aich)