Karkanis was born in Alberta and raised in Toronto. She is of Greek and Egyptian descent. In 2005, she made her screen debut in an episode of 1-800-Missing and later had a number of guest-starring, recurring and regular roles on Canadian television shows. She also had regular voice roles in Skyland, MetaJets and Total Drama: Revenge of the Island. She has a regular voice role in Wild Kratts as Aviva Corcovado.
Karkanis co-starred in several horror films, including Saw IV (2007), Repo! The Genetic Opera (2008), Saw VI (2009), Survival of the Dead (2009), and The Barrens (2012). She also appeared in direct-to-video action films The Art of War II: Betrayal (2008), and Sacrifice (2011). On television, she was a regular cast member in the first season of Canadian teen drama The Best Years in 2007, in The Border from 2008 to 2010, and in the short-lived comedy series Almost Heroes in 2011. She also had a recurring role in Lost Girl from 2011 to 2012.
Karkanis starred in the AMC drama series Low Winter Sun in 2013. In 2014, she was cast as a series regular in the Lifetime post-apocalyptic drama series, The Lottery. In 2015, she began playing the role of Octavia Muss on The Expanse. In 2018, Karkanis started playing Grace Stone on the NBC TV series Manifest.

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