In 1976, the city of Greenville adopted the Council-Manager system of governance. The mayor and six council members make up the Greenville City Council. The mayor and two council members are chosen from single-member districts, while the remaining council members are elected at large. Criminal misdemeanors, traffic offenses, and city ordinance violations are all handled at Greenville Municipal Court. Knox H. White, the city’s mayor as of 2021, has held office since December 1995.

The Greenville Police Department began as the Greenville Police Force in 1845. The Greenville Police Force became the Greenville Police Department in 1876. The Greenville Police Department and the Greenville County Sheriff’s Department relocated into the Greenville County Law Enforcement Center in 1976. The Greenville Police Department employs roughly 241 people and has 199 sworn officers.

Greenville is represented in the South Carolina House of Representatives by districts 22–25, as well as state Senate districts 6–8. The city is in the 4th congressional district of South Carolina, which has been represented by William Timmons since 2019.