Three-term incumbent Hōdō Nakamura ran for re-election for a fourth four-year term, announcing his intentions on the final session of the Nagasaki Prefectural Assembly for 2021 on 21 December.

[2][3] Nakamura had attempted to recruit a successor; but decided to run himself after those efforts fell through.

Nakaumura faced medical doctor Kengo Oishi and businessman Yoshihiko Miyazawa.

After previously endorsing Nakamura in 2010, 2014, and 2018, the prefectural Liberal Democratic Party federation instead voted to endorse the political newcomer Oishi in this election, due to dissatisfaction in Nakamura's governing.

[6][8] Withdrew candidacy Issues in the election included COVID-19-related policies amidst the pandemic, extending the then-upcoming Nishi Kyushu Shinkansen through Saga Prefecture, construction of the Ishiki Dam [ja], and a potential integrated resort facility in the prefecture.