With about 80 members of the Japanese media looking on at Angel Stadium in Anaheim, California, Ohtani beat out an infield single in the first inning, then grounded out to first in the second.
In the fourth inning, Ohtani became the third consecutive Angels batter to take Kikuchi deep. In a span of four pitches, Tommy La Stella and Mike Trout started the inning with back-to-back homers before Ohtani hit the first offering he saw over the left-center-field fence.
The Angels hadn't hit three consecutive homers since September 2016, also against Seattle. A Japanese-born batter hadn't homered off of a Japanese-born pitcher in the majors since July 8, 2009, when Kosuke Fukudome connected off Kenshin Kawakami.
"I was trying to treat it like a normal game and a normal at-bat, but there was something special about it,'' Ohtani said through an interpreter. "I mean, we went to the same high school. I'm glad that we got the results we wanted, though.''
Ohtani celebrated with obvious glee, even flexing his muscles in the dugout -- although he was only mimicking a previous gesture by teammate Kole Calhoun, he said.
"That's the most excited I've seen him on a homer,'' Trout said. "I think I would be, too, if I went to the same high school. I'd be excited, too. I'd never seen him like that. It was pretty cool.''
Kikuchi lasted three more batters before being pulled. Ohtani kept up his hot hitting against reliever Tayler Scott, adding an RBI double in the fifth inning and finished 3-for-5 in the Angels' 12-3 win.
Ohtani, 24, and Kikuchi, 27, attended Hanamaki Higashi High School in Japan but missed each other by a year. They faced off five times in Japan's top league before Ohtani left to begin the next chapter in his revolutionary two-way career.
Although they haven't been able to meet up for dinner yet this year, they've stayed in touch since Kikuchi arrived in the majors one season after Ohtani, the 2018 AL Rookie of the Year.
"I'm very proud of the fact that we faced each other on the highest level in baseball,'' Ohtani said. "Hopefully we get to do it a lot more.''
Kikuchi's ERA is up to 4.99 after he took his third consecutive loss while giving up nine hits and six earned runs to the Angels, who have scored 16 earned runs against him over three starts.
"They hit three home runs off me today, so I didn't like what happened, including Ohtani,'' Kikuchi said through an interpreter. "But I want to make sure next time I go out there and pitch against the Angels, I want to shut them down and do it for the team.''
Seattle manager Scott Servais said of Kikuchi will be OK.
"On the homers, he just didn't get the ball where he wanted to," Servais said. "The ball to Ohtani was just a curveball that stayed up. It happens.''
Information from The Associated Press was used in this report.