From 1976 to 1989, she was the co-host of The Today Show. While not the first female anchor of the show, she became a symbol for professional women, more specifically female journalists, in the 1980s. She shared anchor duties with Tom Brokaw and, later, Bryant Gumbel. Though she had been affiliated with Today long before Gumbel was hired, she was not named the program's primary host upon Tom Brokaw's departure. Instead, Gumbel was brought on as the lead host of the show, with Pauley serving in a deferential co-host capacity.

In 1989, following months of speculation on her future, she announced her resignation from Today in favor of rising star Deborah Norville. The Pauley for Norville switch was a highly publicized incident that led to accusations of ageism from Pauley supporters, who felt it unfair that that the 39-year-old was being sidelined for the younger, more beautiful Norville, who was only in her early thirties.

Pauley remained with NBC after leaving Today, first hosting the short-lived Real Life with Jane Pauley and also serving as deputy anchor for NBC Nightly News.

She co-hosted, with Stone Phillips, Dateline NBC -- NBC's first successful prime time news magazine program ever -- from 1992 to 2003, at which time she announced her retirement. In 2004, she returned to television as host of The Jane Pauley Show, a syndicated daytime talk show. On the show, she discussed, at length, her problems in dealing with bipolar disorder.

Much like her earlier attempt at solo hosting following her Today tenure, The Jane Pauley Show never gained traction in the ratings, and was replaced by Martha Stewart's daytime program Martha. Since her talk show's cancellation, she has neither made appearances on television programs, nor annouced plans to do so in the future.

Pauley is known for revealing very little, if anything at all, on her private life, which made the disclosure of her bipolar disorder all the more unusual. The timing of her announcement—which coincided with the release of her autobiography Skywriting: A Life Out of the Blue and the launch of her daytime talk show—was viewed by some as a publicity ploy, though no one questioned the truthfulness of her announcement.

Pauley is married to cartoonist Garry Trudeau, and they have three children.