A native of Kendall, Florida, a suburb of Miami, Natalie Morales is of Cuban descent. She attended St. Agatha Catholic School while growing up, and then went to Southwest Miami Senior High School. She participated in the University of Miami's Dow Jones Minority High School Journalism Workshop.

Morales had a guest appearance on CSI: Miami in 2006, and played a character in Pimp My Ride that year, a video game version of the MTV television series.Her first major role was in The Middleman, a sci-fi dramedy which aired on the ABC Family network for one season. She starred as Wendy Watson; the series was adapted from the comic book, The Middle Man. Morales also starred in and executive produced a Web series, titled Quitters.

The series was an official selection of the 3rd annual ITVFest (Independent Television Festival) in Los Angeles in August 2008.

In 2009, Morales joined the cast of the USA Network television series, White Collar, for the first season. She portrayed Lauren Cruz, a junior FBI agent. In May 2010, Morales began appearing in the NBC sitcom Parks and Recreation, portraying Lucy, girlfriend of Aziz Ansari's character Tom Haverford and bartender at The Snakehole Lounge, and has recently appeared in a Doctor Who special commenting on the phenomenon of regeneration. Morales appeared in Oliver Stone's 2010 film, Wall Street: Money Never Sleeps, a sequel to his 1987 film Wall Street.

She was cast as Chelsea Handler's best friend in Are You There Vodka? It's Me, Chelsea, but left the series when the cast was replaced for creative reasons.

Morales also appeared on the Aaron Sorkin-created HBO drama, The Newsroom, guest-starring as Kaylee, the girlfriend of Dev Patels character, Neal.

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