In December, he became the 2nd player out of high school in NPB history to reach 100M yen in salary in his third year, after Daisuke Matsuzaka in 2001. His new contract more than tripled his previous salary estimated at 30M yen.

During the July 2014 Mazda All-Star Game, he threw a 162 km/h (101 mph) fastball in the bottom of the 1st inning, setting a new record for the fastest official pitch thrown by a Japanese pitcher, beating the record set by the Yakult Swallows’ Yoshinori Sato in 2010 (161 km/h (100 mph)). The jersey he wore during the game sold for 1,752,000 yen ($17,000), making it the top-seller at the All-Star 2014 Charity Auction. The proceeds were donated to three Tohoku earthquake children’s relief funds.

Shohei Ohtani attended Hanamaki Higashi High School in Iwate Prefecture, Northern Japan. He pitched a 160 km/h (99 mph) fastball as an 18-year-old high school pitcher. He threw the pitch in the Japanese national high school baseball championship tournament, commonly called Summer Koshien. In the 2012 18U Baseball World Championship, Ohtani had an 0–1 win–loss record with 16 strikeouts, eight walks, five hits, five runs, and a 4.35 earned run average in 10⅓ innings pitched.

Ohtani expressed a desire to move directly to the major leagues after high school and received interest from numerous teams including the Texas Rangers, Boston Red Sox, New York Yankees and Los Angeles Dodgers. On October 21, 2012, he announced that he would pursue a career in Major League Baseball rather than turn professional in Japan. The Hokkaido Nippon-Ham Fighters decided to draft him anyway, knowing that there was a high likelihood he would not play for them. But after a month-long negotiation between him and the Fighters, Ohtani announced that he would sign with the Fighters and spend some years in Japan before a possible MLB move. He was assigned the jersey number 11, previously worn by Yu Darvish.

Ohtani made his debut at age 18 in the Hokkaido Nippon-Ham Fighters’ season-opening game on March 29, 2013, playing as a right fielder. He was selected for a Pacific League roster spot for the 2013 All-Star Game. As a pitcher, he finished the season with a 3–0 record in 11 starts. Ohtani was used as a rookie in both the outfield (leading the Fighters with 51 games in right) and as a pitcher. The unusual two-way role was historic. He was the second Nippon Pro Baseball rookie drafted out of high school the previous year, to be used as both a pitcher and position player, following Kikuo Tokunaga in 1951; Ohtani was the first to start in both roles. He was the first NPB pitcher since Takao Kajimoto in 1963 to bat 3rd, 4th or 5th and the first rookie hurler to do so since Junzo Sekine in 1950. He was the second player, following Osamu Takechi (also 1950), to start a game at pitcher, bat in the heart of the order (3rd through 5th) and get a hit and RBI in that game. He missed time during the year with a right ankle sprain and right cheekbone fracture.

The fans voted the high-profile rookie into the All-Star Game despite mediocre numbers. For the season, he was 3–0 with a 4.23 ERA with 33 walks to 46 K in 61 2/3 IP and hit .238/.284/.376 in 204 plate appearances. He had 7 outfield assists to one error. His 8 hit batsmen tied Manabu Mima, Tadashi Settsu, Hideaki Wakui and Ryoma Nogami for 5th in the 2013 Pacific League. He did get 4 of the 233 votes for the 2013 Nippon Professional Baseball Rookie of the Year Award (Pacific League), tying Tatsuya Sato for a distant second behind Takahiro Norimoto.

2015 marked Ohtani’s third professional season (and second full season). Though his offensive production declined somewhat (5 home runs), his performance on the mound was among the best in the league, earning him the starter role in the 2015 All-Star Game and the pitching spot in the end-of-year Pacific League Best Nine awards. Ohtani started 2015 NPB All-Star Game 1 for the PL. He went two innings and fanned two, allowing one run (on a double by Yoshitomo Tsutsugo and a single by Jose Lopez), relieved by Nishi with a 1–0 deficit. The PL would lose 8–6 but he got a no-decision. He finished the season 15–5 with a 2.24 ERA, 196 strikeouts and only 100 hits in 160 2/3 IP. He led the PL in ERA (.14 over Nishi), tied Wakui for the most wins and was second in strikeouts (19 behind Norimoto, though he threw 34 fewer innings). He rarely played the field but did see some action at DH, hitting .202/.252/.376 with 5 HR in 109 AB. He made the Best Nine as the PL’s top hurler. He finished third in MVP voting again, placing behind Yanagita and Shogo Akiyama for the 2015 Pacific League MVP. Ohtani placed third in MVP voting (first among pitchers) and was one of three candidates considered for the 2015 Sawamura Award, given annually to the top pitcher in either league.

Ohtani was dominant for the Japanese national team in the 2015 Premier 12. He hit 100 mph while blowing away eventual champion South Korea (10 K, 2 H, 2 BB, 0 R in 6 IP) before Norimoto relieved. Facing South Korea again in the semifinals, he was even sharper (11 K, 0 BB, 1 HB, 1 H in 7 IP). He did not give up a hit until Keun-woo Jeong singled in the 7th and had the most whiffs in a game for the first Premier 12 ever. Norimoto relieved with a 3–0 lead but he and two other relievers combined to allow four in the 9th to blow it as Japan fell in a shocking defeat. He led the event in ERA (Scott Diamond had 12 innings with a 0.00 ERA to Ohtani’s 13) and strikeouts (one ahead of Chun-Lin Kuo) while allowing the lowest average by a starting pitcher. He was named the All-Star SP for the event (Sho Nakata was the only other member of Samurai Japan to be picked for the All-Star team).

In the 2015 Premier12, Ohtani earned a bronze medal with the Samurai Japan National Baseball Team. He was the ace of Japan’s pitching staff, which featured Kenta Maeda. As the number one starter, Ohtani made two pitching appearances for Japan, both against the Republic of Korea, winning Game 1 of the opening round and getting a no-decision in the semifinals. Ohtani was subsequently named to the 2015 World Baseball Softball Confederation All-World Team and was named the 2015 WBSC Baseball Player of the Year.

In 2016, Ohtani had a breakout season as a hitter. In 104 games and 382 plate appearances, he hit 22 home runs. He also hit 18 doubles, 67 RBI, batted .322 with an OBP of .416, scored 65 runs and had 7 stolen bases. He won the Best Nine award as the designated hitter. Ohtani was the same dominant pitcher on the mound. In 21 games pitched, he had a career low in ERA at 1.86. He had a 10–4 record, struck out 174 batters in 140 innings with 4 complete games and one shutout. He also won the Best Nine award as a pitcher and won the Pacific League MVP. He got nearly double as many votes as any other pitcher for the PL for the 2016 NPB All-Star Game; he had 300,025 while #2 Shota Takeda had 158,008. He could not pitch in the event due to a blister on his finger but wound up starring as a DH. In Game 1, he batted for DH Yuya Hasegawa and lined out in the 8th against Scott Mathieson. Starting at DH and hitting 5th in Game 2, he homered off Shoichi Ino in the 5th to start the PL comeback from a 3–0 deficit. He singled against Ryo Akiyoshi in the 7th and scored on a hit by Kenta Imamiya for a 4–3 lead. Coming up with a 5–4 deficit in the 8th, he singled off Shinji Tajima to bring in Shogo Akiyama with the tying run. He thus produced three of the PL’s five runs in the 5–5 tie, earning him game MVP honors. He hit 165 km/h (102.5 mph) on the radar gun during the year, setting a new NPB record.

In 2017, he played in 65 games, hitting .332 with 8 homers and 31 RBIs while going 3–2, 3.20 with 29 strikeouts on the mound. In September, it was revealed that Ohtani would ask to be posted at the end of the season in order to play in Major League Baseball in 2018. However, before that could happen, he had surgery on his right ankle in early October. The injury had originally occurred in the 2016 Japan Series, and had cost him a chance to play in the 2017 World Baseball Classic in addition to restricting his playing time during the season. There was a question as to whether or not NPB and MLB could come to a posting agreement. Both sides did come to an agreement on November 21, 2017.

On December 8, 2017, Ohtani agreed to a deal with the Los Angeles Angels. The deal was finalized the next day. On December 13, it was revealed that Ohtani was diagnosed with a first-degree UCL sprain in his right elbow. He received a platelet-rich plasma injection to treat the injury.

On September 3, 2018, ESPN announced that doctors recommended that Ohtani undergo Tommy John surgery, after an MRI showed new damage to his UCL. The Angels announced on September 25 that Ohtani had agreed to the procedure, which might potentially keep him off the mound until 2020. On October 1, Angels general manager Billy Eppler announced that Ohtani underwent successful Tommy John surgery. On November 12, he was named the American League Rookie of the Year.

On May 7, 2019, Ohtani played in his first game with the Angels since undergoing Tommy John surgery, batting as a designated hitter against the Detroit Tigers. In a June 13 game against Tampa Bay, Ohtani became the first Japanese-born player to hit for the cycle in MLB history. On September 12, Ohtani’s 2019 season prematurely ended after it was revealed that he needed surgery to repair a bipartite patella. He finished the season batting .286/.343/.505 with 18 home runs, 62 RBIs, and 12 stolen bases in 106 games.

On July 24, 2020, Ohtani was the first ever automatic player on 2nd base in an official MLB game at the start of the 10th inning as part of one of the new 2020 MLB season rules in a game against the Oakland Athletics. He was thrown out in a rundown.

On July 26, 2020, Ohtani returned to the mound against the Oakland Athletics, making his first pitching appearance since September 2018. It did not go well as planned, as he allowed 5 runs and was removed from the mound without recording an out, starting his season with a loss and an infinite ERA. After his second start of the season against the Houston Astros, Ohtani began to experience discomfort in his right arm, and it was eventually revealed that he had a flexor strain in his right elbow after undergoing an MRI. Angels manager Joe Maddon later stated that Ohtani wouldn’t pitch for the rest of the season.