| Ella Beatty | Lizzie Borden | Lizzie Borden (1860–1927), the youngest daughter of the Fall River household — accused of the 1892 killings and acquitted at trial. | Leads the season. Its central question — did she do it? — is the same one the 1893 jury declined to answer with a conviction. |
| Vicky Krieps | Bridget “Maggie” Sullivan | Bridget Sullivan (1866–1948), the Bordens' live-in maid at the time of the deaths. | The series leans on the maid's vantage point inside the household — a perspective the historical record barely preserved. |
| Charlie Hunnam | Andrew Borden | Andrew Borden (1822–1892), Lizzie's father and a prosperous Fall River businessman. | Hunnam also played Ed Gein in Monster Season 3 — a rare two-season, two-role anthology double. |
| Rebecca Hall | Abby Borden | Abby Borden (1828–1892), Lizzie's stepmother. | The distance between stepmother and stepdaughter is a recurring theme in accounts of the household; the series dramatizes it. |
| Billie Lourd | Emma Borden | Emma Borden (1851–1927), Lizzie's older sister. | Emma stood by Lizzie through the arrest and trial; the show draws on the family's private divisions. |
| Jessica Barden | Nance O'Neil | Nance O'Neil (1874–1965), a stage actress who became close friends with Lizzie in the years after the trial. | Their friendship fed decades of speculation; the season draws on that later chapter. |
| Sarah Paulson | Aileen Wuornos | Aileen Wuornos (1956–2002), an American serial killer executed in Florida in 2002. | A cross-era role: Wuornos belongs to a later century, not the 1892 Fall River household. |