Pickler was born in Flint, Michigan to Donald and Marcy Pickler. She grew up in Rector, Arkansas, and later moved to Burton, Michigan, where she attended Bentley High School. In 1998, she graduated from Michigan State University with a degree in journalism. In 2007 she married Eric Conner, an employee of Fox News.
Pickler was hired by the Detroit offices of Associated Press in 1998 shortly after graduating from Michigan State University. In March 2000, she transferred from the Lansing bureau to the Washington, D.C. bureau where she won the annual John L. Dougherty Award for her work covering the Firestone and Ford tire controversy. 
AP promoted Pickler to cover national political issues in December 2002. She was the lead reporter covering the Democratic Party candidates in the 2004 United States Presidential Election. Pickler was criticized by liberal bloggers for her critical coverage, which they called "Nit Picklering," although candidate Howard Dean praised her in his book as one of a few "outstanding journalists" in a chapter criticizing media coverage of his candidacy overall.
After that election, Pickler worked as a White House correspondent until September 2006, leaving to cover national politics, including the 2008 United States Presidential Election. President Bush bid her farewell personally, saying: "Nedra, baby, I’m gonna miss you. I’m sad you’re leaving." In January,2007 she wrote an article investigating Senator Barack Obama's childhood education in Indonesia. Based on interviews with some of Obama's childhood friends and teachers, she reported that, contrary to some rumors then in circulation, he had been educated in Roman Catholic and public schools. On March 27, 2007, Pickler wrote that Democratic presidential candidate Barack Obama (who had declared his candidacy February 10) had "delivered no policy speeches and provided few details about how he would lead the country" in his campaign up to that point. University of Texas at Austin head football coach Mack Brown once scolded Pickler when she tried to ask Obama a question during a football stadium tour.
At a press conference after he won the 2008 election, Obama called on Pickler to pose the first question to him as president-elect. She returned to the White House to cover his presidency before resigning from the AP in 2015 to work as a managing director at The Glover Park Group.
- "Nedra Pickler, Eric Conner". The New York Times. November 25, 2007. Retrieved May 17, 2011.
- Foren, John (June 21, 2008). "Flint -area mom of presidential campaign reporter is plenty proud, says Flint Journal columnist John Foren". Flint Journal.
- Bao, Robert (Spring 2007). "Nedra Pickler: Road to the White House". MSU Alumni Magazine. Michigan State University Alumni Association. Retrieved May 17, 2011.
- Editor & Publisher (1 August 2001). "APME Presents Annual Awards".
- YGLESIAS, MATTHEW (20 January 2004). "Nit Picklering". The American Prospect.
- Dean, Howard (January 9, 2006). You Have the Power: How to Take Back Our Country and Restore Democracy in America. Simon & Schuster. p. 141. ISBN 0743291492.
- Austin American-Statesman. 25 September 2006.  A blog by Ken Herman
- Pickler, Nedra (2007-01-24). "Obama challenges allegation about Islamic school". San Diego Union-Tribune. Retrieved 2008-02-10.
- Pickler, Nedra (for Associated Press). 27 March 2007. Is Obama All Style and Little Substance?
- Gavin, Patrick (26 February 2008). "Coach Brown Scolds Pickler". FishbowlDC.
- Sweet, Lynn (7 November 2008). "President-elect Obama first press conference. Transcript". Chicago Sun-Times.
- Hazley, Greg (6 July 2015). "AP White House Scribe Pickler Heads to PR". O'Dwyer's.