Sloyan first appeared the 2003 independent feature film My Life with Morrissey as a florist. She continued to appear in a few short films such as No Shoulder, Shamelove, and Autodoc. In 2009, she produced and starred in the short film Plus One. Sloyan has also guest-starred in several television series such as The Beast, The Forgotten, Law & Order: LA, and NCIS. She played a recurring role as a White House employee named Jeannine Locke in the first three seasons of Scandal. She also guest-starred in another ShondaLand production titled Private Practice in 2010. Sloyan continued to appear in smaller films, including In the Key of Eli, Tape 407, and the television movie Murder in Mexico: The Bruce Beresford-Redman Story.
In 2014, Sloyan guest-starred in four television series Castle, Parks and Recreation, Hawaii Five-0, and Rizzoli & Isles. She began a recurring role in the ShondaLand production Grey's Anatomy as Dr. Penelope Blake. She first appeared in the eleventh season episode "How to Save a Life", which included the death of lead character, Derek Shepherd, played by Patrick Dempsey. She appeared again in the 12th season, including the show's 250th episode "Guess Who's Coming to Dinner", which was mostly focused on Sloyan's character.
On stage, Sloyan acted at the Geffen Playhouse and the Segerstrom Center for the arts. She received the LADCC and LA Weekly awards for her performance in Munched.
|2003||My Life with Morrissey||Florist||Independent feature film|
|2005||No Shoulder||Bobbie||Short film|
|2009||Plus One||Lindsay||Short film, credited as producer|
|2011||In the Key of Eli||Megs|
|2013||Do You Have a Cat?||Marissa||Short film|
|2009||The Beast||Grace Morton||Episode: "No Turning Back"|
|2009||The Forgotten||Nurse||Episode: "Railroad Jane"|
|2010||Law & Order: LA||Rachel Forester||Episode: "Echo Park"|
|2011||The Cape||Television reporter||Episode: "Endgame"|
|2011||NCIS||Emily Goodwin||1 episode|
|2012–2014||Scandal||Jeannine Locke||Recurring role (8 episodes)|
|2013||The Fosters||ER Doctor||Episode: "Vigil"|
|2014||Castle||Pam Clark||1 episode|
|2014||Parks and Recreation||Erica||Episode: "New Slogan"|
|2014||Hawaii Five-0||Sarah Richmond||1 episode|
|2014||Rizzoli & Isles||Alex Ruebens||Episode: "If You Can't Stand the Heat"|
|2015–2016||Grey's Anatomy||Dr. Penelope Blake||Recurring role|
|2015||Criminal Minds||Tracy Senarak||Episode: "The Witness"|
|2015||Murder in Mexico: The Bruce Beresford-Redman Story||Gretchen||Television movie|
|2017||The Good Doctor||Mrs. Gallico||Episode: "Point Three Percent "|
|2018||The Haunting of Hill House||Leigh||Recurring role|
|2018||SEAL Team||Victoria Seaver||Recurring role|
|2018||The Rookie||Alice Sheldon||Season 2 Episode 4 "Warriors and Guardians"|
|2020||Helstrom||Jolene Spivey||2 episodes|
|2021||Midnight Mass||Bev Keane||Main role|
|2022||The Midnight Club||Shasta||Main role|
|TBA||The Fall of the House of Usher||Filming|
|Denotes works that have not yet been released|
- Denninger, Lindsay (October 22, 2015). "Who Plays Penny On 'Grey's Anatomy'? Samantha Sloyan Is The Hospital's Newest Resident". Bustle. Retrieved October 25, 2015.
- "Samantha Sloyan". Geffen Playhouse. Archived from the original on September 24, 2021. Retrieved September 24, 2021.
- Romanchick, Shane (January 31, 2022). "Mike Flanagan's 'The Fall of the House of Usher' Officially Begins Production". Collider. Retrieved February 4, 2022.