She is the younger of the sororal twin daughters of the 43rd U.S. President George W. Bush and former First Lady Laura Bush, and a granddaughter of the 41st U.S. President George H. W. Bush and former First Lady Barbara Bush. She and her sister Barbara were the first twin children of a U.S. President.

After meeting during her father's 2004 presidential campaign, Bush and Henry Chase Hager (born May 9, 1978) became engaged in August 2007. Before proposing, Hager asked President Bush for permission to marry his daughter. Their relationship became public when the two appeared together at a White House dinner for The Prince of Wales and The Duchess of Cornwall in November 2005. Henry Hager attended St. Christopher's School in Richmond, Virginia, and holds an MBA from the Darden Graduate School of Business Administration at the University of Virginia. He worked as a U.S. Department of Commerce aide for Carlos Gutierrez and as a White House aide for Karl Rove. He is the son of former Virginia Republican Party Chairman John H. Hager, who previously served as Lieutenant Governor of Virginia and as the U.S. Department of Education Assistant Secretary under George W. Bush. The wedding took place during a private ceremony on May 10, 2008, at her parents' Prairie Chapel Ranch near Crawford, Texas.

Hager was born at Baylor University Medical Center in Dallas, Texas, and named after her maternal grandmother, Jenna Hawkins Welch. While living in Dallas, she and her sister attended Preston Hollow Elementary School and then The Hockaday School. In 1994, after her father was elected Governor of Texas and the family moved to Austin, Texas, Bush was a student at St. Andrew's Episcopal School, and attended Austin High School from 1996 until her graduation in 2000.

With her father becoming President in 2001, she attended the University of Texas at Austin and took summer classes at New York University. She was a legacy member of Kappa Alpha Theta, her mother's sorority. While there, Jenna and her sister Barbara made national headlines when they were both arrested for alcohol-related charges twice within 5 weeks: on April 29, 2001, Jenna was charged with a misdemeanor for possession of alcohol under the age 21 in Austin. On May 29, 2001, Jenna was charged with another misdemeanor—attempting to use a fake ID (with the name "Barbara Pierce", her paternal grandmother's maiden name) to purchase alcohol. She pleaded no contest to both charges. Jenna Bush graduated from UT Austin with a degree in English in 2004.

She asked her father not to run for President in 2000: "Oh, I just wish you wouldn't run. It's going to change our life." Her father told her that he and her mother needed to live their lives. In the winter of 2003, however, she decided to become involved in the 2004 campaign. In response to this decision, she made media appearances during the summer of 2004 prior to the election. She and her sister made several joint public appearances, including giving a speech to the Republican Convention on August 31, 2004. She made headlines when she was found sticking her tongue out to media Photographers at a campaign stop in St. Louis. Jenna and Barbara took turns traveling to swing states with their father and also gave a seven-page interview and photo shoot in Vogue.

Before leaving Washington, D.C. in Summer 2006, Hager worked at Elsie Whitlow Stokes Community Freedom Public Charter School for a year and a half as a teacher's aide. She took a leave of absence from the Charter School teaching position to work at a shelter as part of an internship for UNICEF's Educational Policy Department in Latin America, specifically in Panama. After her internship for UNICEF, Hager returned to her position at the charter school in Washington, D.C. She currently works as a part-time reading coordinator at the SEED Public Charter School in Baltimore, Maryland, and contributes a monthly news story about education for the Today show.

In 2007, Hager began marketing a book proposal with the assistance of Robert B. Barnett, a Washington attorney. The title of the book is Ana's Story: A Journey of Hope and it chronicles her experiences working with UNICEF sponsored charities in Latin America, including visits to drought stricken Paraguay in 2006, while working as an intern for United Nations Children's Fund. HarperCollins announced in March 2007 it would publish the book and it was released September 28, 2007, with an initial printing of 500,000 copies. Her share of the profits will go to UNICEF; the remainder will go to the woman whose life is the basis of the book, assisting in the young woman's continuing education. During the book tour, Hager appeared on The Ellen DeGeneres Show; during the interview Hager telephoned her parents. Hager wrote a second book, in conjunction with her mother, which is designed to encourage children to read. The book, entitled Read All About It!, was published on April 22, 2008, also by HarperCollins.

In August 2009, NBC hired Hager as a correspondent and contributor for the Today Show.

Unlike most of her relatives, Hager is not a member of the Republican Party. While registering to vote in New York, she mistakenly registered with the Independence Party of New York while meaning to declare herself a nonpartisan. In 2010, Jenna Bush Hager and Barbara Bush told People that they preferred not to identify with any political party, stating, "We're both very independent thinkers."

On December 12, 2012, Henry and Jenna Hager announced on the Today Show that they were expecting their first child. Their daughter, Margaret Laura "Mila" Hager, was born in April 2013, in New York City. Their second daughter was born in August 2015. She is named Poppy Louise Hager, "Poppy" being President George H. W. Bush's childhood nickname and "Louise" being the middle name of Jenna's maternal grandmother, Jenna Hawkins Welch.

After her father's presidency, Hager became an author, serves as an editor-at-large for Southern Living magazine, and also a television personality on NBC, being featured most prominently as a member of The Today Show as a correspondent. She is also a frequent guest co-host of the fourth hour of the show (Kathie Lee & Hoda), especially since Hoda Kotb began anchoring the main show from 7–9 a.m.