Nelson graduated from Yale in 1978 and Phillips Academy in Andover in 1974. She wrote about books and publishing at the New York Post, the New York Observer, Glamour magazine, and held editorial positions at Self, Inside.com, and Book Publishing Report. Nelson married and had a child and is a fierce advocate for respect for working mothers. Women struggled with ways to juggle careers and families, and stay-at-home moms and working mothers jostled over women's roles in the home, sometimes termed in the media as the Mommy Wars. Nelson wrote:

Nelson, based on a New Year's plan, embarked on an ambitious project to read one book each week and write about it, and the effort morphed into a book entitled So Many Books, So Little Time: A Year of Passionate Reading which was published by Putnam in 2003. While her initial book–a–week plan fell apart almost immediately, according to New York Times book reviewer Ihsan Taylor, the effort was fruitful since the book was seen as a commentary on the "nature of reading itself." Nelson's Future employer, Publishers Weekly, reported that her book revealed her "infectious enthusiasm for literature in general." Writer Augusten Burroughs said Nelson's book was a "smart, witty, utterly original memoir about how every book becomes a part of us."

After a profound economic downturn beginning in 2007 and lasting for the next few years, the publishing industry slumped significantly. Nelson commented in 2008 how layoffs and salary freezes were "sobering".

In 2008, Nelson commented on the intersection of political candidates, books, and television celebrities such as Oprah Winfrey, not knowing that the talk show Celebrity would be her employer within a year. There were several dozen books about then-candidate Obama. Nelson was interviewed on National Public Radio on Winfrey's influence, similar to that of radio personality Imus, in the publishing arena. She described Oprah:

In September 2009, Nelson was appointed book Editor at Oprah's O Magazine. She continued to comment in the media about new forces in publishing such as the new quarterly literary magazine called Electric Literature which allows readers to read in a variety of media, including e-book, iPhone, and audiobook. Nelson applauded the effort saying that "anything that takes the starch out" was good. Generally, Nelson's outlook for the publishing industry is bright and thinks that "in the end readers will win." Sara Nelson appeared with Harry Smith of CBS News on The Early Show. She's also served as moderator for events sponsored by the LA Times Festival of Books.

Nelson identified other trends. Fewer places review books now, unfortunately, but there is more information available to consumers who may not want in-depth literary reviews of a book; rather, they want to know whether it's worth plunking down $25, and that's it. In some respects, according to Nelson, smaller publishers are better off than large houses which have huge budgets devoted to overhead; for Example, Nelson said a small "mom and pop" publisher can do five books a year and be profitable. She still thinks it's tough times for people employed within the industry; she said "You can do all the right things and still lose your job." She thinks business-to-business magazines will become available mostly online, and soon. In the past, self publishing was seen as the "exclusive realm of egomaniacs, eccentrics, and failures," according to a reporter in the Los Angeles Times, but over the past decade or so it's become more popular and somewhat better accepted. Nelson commented in 2010 that there were more instances of publishers picking up a self-published book, although such success stories are still rare. "Publishers are taking self-published books more seriously," she said.

Nelson became editor–in–chief of the trade magazine Publishers Weekly in January 2005. It was a powerful position since the magazine is traditionally regarded as a standard bearer for mainstream critical opinion regarding books. A positive review from Publishers Weekly can bring a big sales boost to an unknown title, and the editor–in–chief's opinion about new books has considerable weight in the publishing industry. New York Times reporter Edward Wyatt suggested that the top job at Publishers Weekly in 2005 involved facing "many challenges".

The first decade of the new century was marked by turbulence within the industry as well as a continuing trend away from serious writing and towards pop culture. Publishers Weekly had enjoyed a "near monopoly" over the past decades but was getting vigorous competition from Internet sites, e-mail newsletters and daily newspapers. The industry was consolidating. Many independent booksellers—a mainstay of Publishers Weekly clientele—were going out of Business. Paid circulation dropped by 3,000 to 25,000 in the mid 2000s. Nelson pushed for significant changes towards modernization, greater use of the Web, and more focus on analytical reporting.

The action sent shockwaves through the industry and was widely covered in prominent newspapers. There was considerable reaction by readers as well. One reader wrote: "Sara Nelson turned Publishers Weekly around!" Another wrote that "Sara Nelson pulled Publishers Weekly into the 21st century with grace, verve, and panache. And I’ve never met such a loud Cheerleader for books and for the book publishing industry."