Mays' first television appearance was on Joey (2004). She made her feature film debut with a supporting role in Red Eye (2005). Her early television work includes appearances on Six Feet Under (2005), Stacked (2005), How I Met Your Mother (2006), Heroes (2006–2009), Pushing Daisies (2007–2009), The Comeback (2005), Entourage (2006), Ghost Whisperer (2006) and Ugly Betty (2006–2010).
Her film credits include Bar Starz (2004), Flags of Our Fathers (2006), Epic Movie (2007), Get Smart’s Bruce and Lloyd: Out of Control (2008) and Paul Blart: Mall Cop (2009). She appeared on House in 2006 and played roles connected to Heroes (2006–2009) and Ugly Betty (2008).
She starred as Emma Pillsbury on the Fox series Glee, which premiered in 2009. She was a series regular for the first three seasons (2009–2012) and appeared as a guest star in seasons four through six (2012–2015). She played the female lead Grace Winslow in The Smurfs (2011).
From 2017 to 2018, she starred as Carol Anne Keane on the NBC series Trial & Error. She appeared on Great News in 2018. In 2022, she appeared in Disenchanted, the sequel to Enchanted.
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