Port St. Lucie is a city in St. Lucie County, Florida, United States. It is the most populous municipality in the county and the seventh-most populous city in Florida with a population of 204,851 at the 2020 census. It is located 125 miles (201 km) southeast of Orlando and 113 miles (182 km) north of Miami. It is a principal city in the Port St. Lucie Metropolitan Statistical Area, which includes St. Lucie and Martin counties, and as of 2021 had an estimated population of 502,521. Port St. Lucie is also a principal city in the Miami-Fort Lauderdale-Port St. Lucie Combined Statistical Area, which had an estimated population of 6,841,100 as of 2021.

St. Lucie County is located in the southeastern portion of the U.S. state of Florida. As of the 2020 census, the population was 329,226. The county's seat is Fort Pierce, while the largest city is Port St. Lucie, making up 62% of the county's population. St. Lucie County is the principal county of the Port St. Lucie, FL Metropolitan Statistical Area.