Luzerne County is a county in the Commonwealth of Pennsylvania. According to the United States Census Bureau, the county has a total area of 906 square miles (2,350 km2), of which 890 square miles (2,300 km2) is land and 16 square miles (41 km2) is water. It is Northeastern Pennsylvania's second-largest county by total area. As of the 2020 census, the population was 325,594, making it the most populous county in the northeastern part of the state. The county seat and most populous city is Wilkes-Barre. Other populous communities include Hazleton, Kingston, Nanticoke, and Pittston. Luzerne County is included in the Scranton–Wilkes-Barre–Hazleton Metropolitan Statistical Area, which has a total population of 555,426 as of 2017. The county is part of the Northeastern Pennsylvania region of the state.

Northeastern Pennsylvania is a region of the U.S. state of Pennsylvania that includes the Pocono Mountains, the Endless Mountains, and the industrial cities of Scranton, Wilkes-Barre, Pittston, Hazleton, Nanticoke, and Carbondale. A portion of this region is located in the New York City metropolitan area. Recently, Pennsylvania tourism boards have described Northeastern Pennsylvania as Upstate Pennsylvania.