Her film work includes the 2009 remake of 1987 thriller The Stepfather and the Brendan Fraser comedy Furry Vengeance (2010). On TV she appeared as succubus Andie Bates on the ABC supernatural crime drama "The Gates". At the 2011 Teen Choice awards, she was nominated as Breakout Star for her titular role in the ABC Family series "The Nine Lives of Chloe King". She has starred in the first season of new horror comedy series created by Ryan Murphy called Scream Queens as Grace Gardner. Most recently Samuels appeared on The Gifted in the role The Stepford Cuckoos (Esme, Sophie and Phoebe).
Samuels is the daughter of Kathy, a producer for unscripted series, and Scott, a U.S. marshal. She has three brothers, Cody, Harrison, and Jack, and one sister, Heather.
- Skyler starred in the first season of Ryan Murphy's Scream Queens in 2015.
- She is one of the six actors to work on both American Horror Story and Scream Queens. The others are Billie Lourd, Cathy Marks, Colton Haynes, Dalton E. Gray and Emma Roberts.
- Some photos from the set of Cult revealed that she was originally going to be in an optometrist sub-plot, however, the scene was removed from the episode.