The Los Angeles Angels two-way star went down to his left knee in the third inning when he homered to center off right-hander Hiroto Saiki. Ohtani homered to center again in the fifth against left-hander Ren Tomida.
Ohtani struck out in his first at-bat and suggested he might have had jet lag after traveling from spring training in the United States.
The game was Ohtani's first for Japan since an exhibition against the Netherlands on Nov. 13, 2016.
The WBC starts Wednesday with two games in Taiwan: Cuba vs. Netherlands, and Panama vs. Taiwan. Japan opens Thursday against China at the Tokyo Dome. Ohtani is expected to be Japan's designated hitter.
Japan won the first two editions of the tournament in 2006 and 2009. The U.S. is defending champion after winning in 2017. The Dominican Republic is considered a favorite.