Rometty was born on July 29, 1957, in Chicago. She is oldest of four children. Her Father left when she was fifteen years old and her mother worked multiple jobs to support her and her siblings. Rometty graduated from the Robert R. McCormick School of Engineering and Applied Science at Northwestern University in 1979 with high honors, receiving a bachelor's degree in computer science and electrical engineering. Rometty was a member of the Kappa Kappa Gamma sorority, eventually serving as its President. She has received honorary doctoral degrees from Rensselaer Polytechnic Institute (2014) and Northwestern University (2015).

In 1979 Rometty married Mark Anthony Rometty, a principal investor in the Bam Oil Company, whom she met at General Motors while working there for two years after college. The couple has no children. In 2014, she became the third female member of the Augusta National Golf Club.

Rometty serves on the Council on Foreign Relations; the Board of Trustees of her alma mater Northwestern University; the Board of Overseers and Board of Managers of Memorial Sloan-Kettering Cancer Center; and is a council member at the Latin America Conservation Council, a subsidiary of The Nature Conservancy. She also served on the Board of Directors of AIG from 2006 until 2009.

On October 25, 2011, IBM announced that she was to be the company's next President and CEO, with Sam Palmisano stepping down but retaining his position as chairman. Rometty's appointment marks the first time a woman has been CEO of IBM. Regarding her promotion, Palmisano stated, "Ginni got it because she deserved it ... It’s got zero to do with progressive social policies."

On September 26, 2012, IBM announced that Rometty was taking on the added role of chair of IBM, as Samuel Palmisano prepared to retire at the end of 2012. Rometty commenced her duty as chair, President, and CEO of IBM on October 1, 2012. One of her goals is to focus company efforts on the cloud and cognitive computing systems, such as Watson, which she had done as of 2018.

Over Rometty's tenure as CEO she has been met by increasing criticism, most notably a confrontation with Mark Cuban, who said, "IBM is no longer a tech company" and "They have no vision", with IBM losing revenue for 10 consecutive quarters at the time of his October 2014 interview. IBM employees have also criticized her for taking pay bonuses despite massive layoffs, as well as for poor performance. Rometty has been named among the worst CEOs by several publications including The Motley Fool, 24/7 Wallstreet, Forbes, and The Wall Street Journal.

In 2014, Rometty was featured in the PBS documentary The Boomer List. In Fortune's September 15, 2015 issue, Rometty ranked third on their Most Powerful Women List. Named the eleventh most powerful woman on the 2016 Forbes list: The World's 100 Most Powerful Women.

Rometty's tenure as CEO has been marked by prestigious awards including by Bloomberg who named her among the 50 Most Influential People in the World, and Fortune naming her among the "50 Most Powerful Women in Business" for ten consecutive years. In 2017 she was ranked No. 10 on Forbes' World's 100 Most Powerful Women. Her tenure as CEO has been met by criticism related to executive compensation, outsourcing, and IBM's 23 consecutive quarters of revenue decline.