Paul Abbott (Shameless, State of Play) and writer Sean Conway (Brilliant Love, Kings of London) have penned the script about a contract killer, hiding the secret that she is a pre-op transsexual.
Sevigny (Boys Don't Cry, Big Love) will play Mia, the killer, whose life is turned upside down when she is sent a letter from her ex Wendy, who reveals that she is dying from cancer and that Mia has fathered a son.
Hit And Miss, a six-part series, will focus on issues of family, sexual identity and killing as Mia visits her new family in West Yorkshire.
Sky Atlantic's Elaine Pyke said: "Chloë Sevigny is an extraordinarily talented actress and we are thrilled to welcome her to her first UK television role on Sky Atlantic HD. Mia is a complex, challenging character and Chloë is the perfect person to bring her to life."
Abbott said: "When Chloë Sevigny signed up to play Mia in Hit And Miss I was thrilled. She's bringing her unique, smart toolbox with her and, together, we will make a great show better.
"And the next big deal was getting the gifted young filmmaker Sean Conway to lend his genius and unique mischief into this, his TV drama debut."
The AbbottVision and Red Production Company series will air exclusively on Sky Atlantic in 2012.