Dewan was born in Hartford, Connecticut, the daughter of Nancy Smith (née Bursch) and Darryll Dewan, who was a running back on the 1972 Notre Dame football team. Her father is of Lebanese and Polish descent (Dewan being an Arabic surname meaning office or bureau) and her mother is of German and English ancestry. She has three brothers, Dawson, Dayne, and Daniel. Her parents divorced when she was young and her mother remarried Claude Smith.

Dewan first appeared in Janet Jackson's "Doesn't Really Matter" video in 2000, and later in "All for You" and the All for You Tour in 2001. Dewan credits working with Jackson for aiding her career, allowing her to later work with many other artists and giving her the experience necessary to co-star in the dance film Step Up. In 2016, Dewan-Tatum modeled as the face of dancewear manufacturer Danskin in a campaign and photo shoot that captured and featured her athleticism as a Dancer.

In 2006, Dewan co-starred with Channing Tatum in Step Up, as well as starring in Take the Lead that same year.

In August 2008, Dewan starred in the Lifetime made-for-television film Fab Five: The Texas Cheerleader Scandal which follows five rule-breaking teens. She portrayed the role of disciplinarian Coach Emma Carr. In November 2009, she appeared in the straight-to-DVD comedy American Virgin alongside Rob Schneider.

Dewan previously dated Justin Timberlake as well as Shane West. In 2005, Dewan met actor Channing Tatum on the set of their film Step Up. They began dating shortly after filming had finished. The couple became engaged in early September 2008 in Maui, and married on July 11, 2009, at Church Estates Vineyards in Malibu, California. Their daughter, Everly Elizabeth Maiselle Tatum, was born on May 31, 2013 in London, England. In an interview on the TV show Late Night With David Letterman, Channing explained that Everly's middle names are from Jenna's grandmother, Elizabeth, and his own grandmother, Maiselle.

Along with friends Reid Carolin, Adam Martingano, Brett Rodriguez and husband Channing Tatum, Dewan started a production company called 33andOut Productions. Their first production is a documentary called Earth Made of Glass that follows Rwandan President Paul Kagame and genocide survivor Jean-Pierre Sagahutu. It premiered at the 2010 Tribeca Film Festival.

In November 2011, Dewan starred in the film The Jerk Theory. This was first released in Germany in 2009. It was later released in the United States in November 2011.

Dewan appeared in the romantic-comedy film 10 Years, produced by her husband Channing Tatum. The film was released on September 14, 2012. That same year, she appeared in the second season of American Horror Story, as Teresa Morrison.

In 2013, Dewan began starring in the Lifetime series Witches of East End as Freya Beauchamp, one of the lead characters. In late 2015, she began a recurring role in the CBS series Supergirl playing Lucy Lane, the sister of Lois Lane and girlfriend of Jimmy Olsen.

Dewan is an animal rights Activist and a vegan. PETA declared her to be one of three "Sexiest Vegans" of 2017.

On April 2, 2018, after nine years of marriage, the couple announced that they were separating.