Tanaka threw 16 consecutive strikes and finished with 49 strikes among 63 pitches.
Tanaka has allowed one run, four hits and struck out four over five innings in two spring training games. He is expected to start in the Yankees third or fourth regular-season game.
This marked the first time Tanaka pitched in the Yankees simulated-game format, which uses only a pitcher, catcher and hitter.
The right-hander was 24-0 with a 1.27 ERA last year while leading the Rakuten Golden Eagles to their first Japan Series title. He is scheduled to pitch Sunday against Atlanta.
Tanaka said the simulated games he pitched during spring training in Japan were during intrasquad matchups.
"Obviously, it's part of practicing," he said. "You're throwing against your own people. Some of the adjustments that I was able to make today, I just want to see if I can do that in a real game."
Jake Cave hit the homer off Tanaka, and Cito Culver had two singles.
"It was fun. It was cool," Cave said. "I guessed right on one of the pitches."