Pittsylvania covers 978 square miles — 969 of land and 9 of water — making it the largest county in Virginia by land area and the second-largest by total area. The county wraps around the independent city of Danville on three sides; Danville sits at its southern border with North Carolina, otherwise surrounded by Pittsylvania. The Roanoke River, here called the Staunton, defines the northern boundary, separating Pittsylvania from Bedford County across Smith Mountain Lake. The Banister River runs through the middle. The Dan River drains the south. The county seat is Chatham, named like the county itself for William Pitt. The 2020 census counted 60,501 residents — a county roughly three-quarters white and one-fifth African American, with a median age over 47 and a quarter of households consisting of someone living alone.

Pittsylvania's early colonial history is the history of an economy that struggled to build towns. Historian Maud Clement, writing in her History of Pittsylvania County, observed that the early settlers had intended to found towns and largely failed to do so. The land was sparsely commercial, and the plantation settlements along the rivers — particularly at ferry crossings — already provided whatever marketing and purchasing services the region needed. The largest of these informal centers belonged to Sam Pannill, a Scots-Irishman who set up a plantation town at Green Hill on the north side of the Staunton River in Campbell County in the late 18th century. The economy was tobacco-dominated and depended on a growing population of enslaved people who did the cultivation, processing, and transport. Pittsylvania was, in Clement's words, a county without towns or a commercial center until Danville emerged. The relationship between the planters of Pittsylvania and the merchants of Danville defined both places through the antebellum period.

Buried beneath a corner of Pittsylvania County, near the unincorporated community of Coles Hill, is the largest undeveloped uranium deposit in the United States — the seventh largest in the world. Estimates of the resource have suggested values in the billions of dollars. Virginia has maintained a moratorium on uranium mining since 1982, and successive owners of the Coles Hill site have lobbied to lift it. The community has divided. Supporters cite jobs and revenue. Opponents cite the Dan River watershed, the Roanoke Rapids reservoir downstream that supplies drinking water to a substantial population, and the long memory of mining disasters elsewhere. The moratorium has held. The uranium remains in the ground.

Pittsylvania has been a Republican stronghold since the 1960s. The last Democratic presidential candidate to carry the county was John F. Kennedy in 1960, although the third-party segregationist George Wallace won it in 1968. The county is divided into seven districts — Banister, Callands-Gretna, Chatham-Blairs, Dan River, Staunton River, Tunstall, Westover — and a sprawling list of unincorporated communities with names that read like a frontier gazetteer: Tightsqueeze, Mount Cross, Climax, Java, Whitfield, Worlds, Pickaway, Sutherlin. The three incorporated towns are Chatham, Gretna, and Hurt. The county's three census-designated places are Blairs, Motley, and Mount Hermon. From the air, what dominates is space — the longest stretch of unbroken Virginia farmland and pine forest you will find east of the Blue Ridge.