Raphael was born and raised in Rockville Centre, New York, to Diane and John Raphael, where she graduated from South Side High School in 1998. She is of Irish descent, and was raised Catholic. She has two older sisters, Lauren and Deanna.
Raphael attended New York University (NYU), where she studied acting at NYU's Tisch School of the Arts and the Stella Adler Studio of Acting. After graduating from NYU in 2002, Raphael and her best friend from college, Casey Wilson, studied improvisational comedy at the Upright Citizens Brigade Theater in New York City, where they would eventually run their two-woman sketch show for a number of years. Performing the long-running stage show opened doors for them as writers.
Raphael began her comedy career writing and performing with the Upright Citizens Brigade Theatre (UCB) in New York and later in Los Angeles. Among her best known work at UCB was the long-running sketch show Rode Hard and Put Away Wet, written and performed alongside her comedy partner and best friend Casey Wilson; the stage show ran from 2003 to 2006 in New York and Los Angeles and was an official selection at 2005's US Comedy Arts Festival in Aspen, Colorado. Raphael and Wilson's comedic partnership has since branched out into an active writing career in film and television; they co-wrote their first screenplay for the comedy Bride Wars, in which they also appeared in supporting roles.

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