Mayer developed a passion for computers while at Stanford University, earning a Bachelor of Science degree in symbolic systems and a Master of Science degree in computer science with a specialization in artificial intelligence. During her studies, Mayer taught undergraduate courses in computer programming, earning two teaching awards for her contribution to undergraduate education. But it was perhaps her research internships at Stanford University and the Union Bank of Switzerland's research lab in Zurich that helped her net 14 job offers fresh out of grad school.

Mayer's 14th job offer came from Google founders Larry Page and Sergey Brin, who quizzed her on artificial intelligence while sitting at a ping-pong table that the company used for conferences. In 1999, Google wasn't yet an Internet search giant. In fact, the company had only 19 employees. Upon accepting an offer to lead Google's user interface and Web server teams, Mayer became the company's 20th employee and its first female engineer.

Her tenure at Google involved work on some of the company's most recognizable and successful products, including Google Maps, Google Earth, Street View, Google News and Gmail. Known as a fashionista with an eye for design, Mayer is widely credited for the unique look and feel that has come to characterize the Google experience. For example, she was responsible for approving each "doodle" (the custom logos commemorating holidays and events) appearing on the Google home page.

Mayer spent more than a decade at Google accumulating accolades for her work ethic, eye for detail and vision. In July 2012, she was appointed president and CEO of Yahoo!, a position she held for five years. On June 13, 2017, Mayer announced her resignation. During her tenure, she helped create $43B in market capitalization, triple Yahoo! stock, grow mobile users to over 650 million, build a $1.5B mobile ad business, and transform Yahoo's culture.

On 8 November 2017, along with several other present and former corporate CEOs, Mayer testified before the United States Senate Committee on Commerce, Science, and Transportation regarding major security breaches at Yahoo during 2013 and 2014.

After leaving Yahoo! Mayer started Lumi Labs in 2018 with her former colleague, Enrique Munoz Torres. The company is based in Palo Alto, California and is focused on artificial intelligence and consumer media. In 2020, she announced the launch of Sunshine, a consumer apps start-up.

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