Oh managed to make the High School Team. In 1957, Waseda Jitsugyo High School made it to the Spring Koshien Tournament with the second-year Oh as its ace pitcher. Before the tournament started, Oh suffered serious blisters on two fingers of his pitching hand. Oh pitched the entire first game at Koshien and won. The next day, Oh pitched another complete game and earned the victory, but the blisters worsened. Oh faced the prospect of pitching two more games—on back-to-back days—for the championship with injuries. Oh pitched and won another complete game, enduring the pain.

In 1959, he signed his first professional contract as a pitcher for the Yomiuri Giants. However, Oh was not a strong enough pitcher to succeed professionally and soon switched to first base, working diligently with coach Hiroshi Arakawa to improve his hitting skills. This led the development of Oh’s distinctive “flamingo” leg kick. His batting average jumped from .161 in his rookie season to .270 in 1960, and his home runs more than doubled. His performance dipped slightly in both statistical categories in 1961, but Oh truly blossomed in 1962, when he hit 38 home runs.

In 1964, Oh hit 55 home runs, a single-season record he owned for 38 years until it was tied by Alex Cabrera in 2002. Oh surpassed 50 home runs in a season two other times, in 1973 and 1977.

Oh became friends with Hank Aaron, his contemporary in Major League Baseball. The two squared off in a home run derby before an exhibition game at Korakuen Stadium on 2 November 1974, after Aaron eclipsed Babe Ruth’s home run record. By that time, Oh was running away with the Japanese home run record, having become the first Japanese baseball player to hit 600 career home runs that year. Aaron won, 10-9.

Sadaharu Oh retired in 1980 at age 40, having amassed 2,786 hits (third after Isao Harimoto (Jang Hoon) and Katsuya Nomura), 2,170 RBIs, a lifetime batting average of .301, and 868 home runs.

In 1985, American Randy Bass, playing for the Hanshin Tigers, came into the last game of the season against the Oh-managed Giants with 54 home runs. Bass was intentionally walked four times on four straight pitches each time. Bass reached over the plate on the fifth occasion and batted the ball into the outfield for a single. After the game, Oh denied ordering his pitchers to walk Bass, but Keith Comstock, an American pitcher for the Giants, later stated that an unnamed Giants coach had threatened a fine of $1,000 for every strike that any Giants pitcher threw to Bass. The magazine Takarajima investigated the incident and reported that the Giants front office had likely ordered the team not to allow Bass an opportunity to tie or break Oh’s record. For the most part, the Japanese media remained silent on the incident, as did league commissioner Takeso Shimoda.

Sadaharu Oh was the assistant manager of the Yomiuri Giants between 1981 and 1983. He became the manager of the Yomiuri Giants between 1984 and 1988. He led the Giants to one Central League pennant in 1987.

In 1995, he returned to baseball as the manager of the Fukuoka Daiei Hawks (later the Fukuoka SoftBank Hawks). Oh led the Hawks to three Pacific League pennants in 1999, 2000 and 2003, and two Japan Series titles in 1999 and 2003.

In 2001, American Karl “Tuffy” Rhodes, playing for the Osaka Kintetsu Buffaloes, hit 55 home runs with several games left. The Buffaloes played the Oh-managed Fukuoka SoftBank Hawks on a late weekend series in Fukuoka. Rhodes was intentionally walked during each at-bat. Hawks catcher Kenji Johjima could be seen grinning as he caught the intentional balls. Again, Oh denied any involvement and Hawks pitching coach Yoshiharu Wakana stated that the pitchers acted on his orders, saying, “I just didn’t want a foreign player to break Oh’s record.” Rhodes completed the season with 55 home runs. Hawks pitcher Keisaburo Tanoue went on record saying that he wanted to throw strikes to Rhodes and felt bad about the situation.

Oh was married to Kyoko Oh (王恭子, Ō Kyōko), and had three daughters with her. Kyoko died of stomach cancer in December 2001 at age 57, the same illness he had in 2006. Their second daughter, Rie (born in 1970), is a sportscaster and presenter on the J-Wave radio network.

In 2002, Venezuelan Alex Cabrera hit 55 home runs with five games left in the season and his team played Oh’s Hawks. Oh told his pitchers to throw strikes to Cabrera, but most of them ignored his order and threw balls well away from the plate. After the game, Oh stated, “If you’re going to break the record, you should do it by more than one. Do it by a lot.” In the wake of the most recent incident involving Cabrera, ESPN listed Oh’s single-season home run record as #2 on its list of “The Phoniest Records in Sports”.

In 2006, Oh managed the Japan national baseball team, winning the championship in the inaugural 2006 World Baseball Classic over Cuba.

On July 5, Oh announced that he was taking an indefinite leave of absence from the Hawks to combat a stomach tumor. On July 17, 2006, Oh underwent laparoscopic surgery to remove his stomach and its surrounding lymph nodes. The surgery was considered to be a success. Although the tumor was confirmed to be cancerous, it was caught in early stages. He returned to coaching the Fukuoka SoftBank Hawks, although he announced he would retire at the end of the 2008 season as manager (but remain as Hawks’ GM). He retired as a manager in 2008.

Wladimir Balentien, a Curaçaoan born player, broke Oh’s home run record on September 15, 2013, by hitting his 56th and 57th home runs of the season in a game against the Hanshin Tigers.