Powell Jobs grew up in West Milford, New Jersey. She earned a B.A. in Political Science from the University of Pennsylvania School of Arts and Sciences and a B.S. in Economics from the Wharton School of the University of Pennsylvania in 1985. She received her M.B.A. from the Stanford Graduate School of Business in 1991.

In October 1989, Steve Jobs gave a "View from the Top" lecture at Stanford Business School. Laurene Powell was a new MBA student and snuck to the front of the lecture and started up a conversation with Steve who was seated next to her. They ended up having dinner together that night. A year and a half later on March 18, 1991, they married in a ceremony at the Ahwahnee Hotel in Yosemite National Park. Presiding over the wedding was Kobun Chino Otogawa, a Zen Buddhist monk. Their son, Reed, was born September 1991, followed by daughters Erin in 1995 and Eve in 1998.

In 1997, Powell Jobs and Carlos Watson co-founded College Track, a nonprofit organization in East Palo Alto to improve high school graduation, college enrollment, and college graduation rates for "underserved" students. Of College Track's high school graduates, many of whom are first-generation college students, approximately 90 percent attend four-year colleges and 70 percent finish college in six years, whereas the national average for first-generation college students is 24 percent. College Track has facilities in East Palo Alto, Sacramento, San Francisco, Oakland, Watts, Boyle Heights, New Orleans, Aurora, Colorado and Denver. "We have a wait list of five cities where we’d like to open up centers," Powell Jobs has said. "We want to keep our standards high, though, and are reluctant to grow through franchising or through dissemination of our curriculum and training.”

On October 5, 2011, at the age of 56, Steve Jobs, the CEO of Apple, died due to complications from a relapse of his previously treated islet-cell neuroendocrine pancreatic cancer. Powell Jobs inherited the Steven P. Jobs Trust, which as of May 2013 had a 7.3% stake in The Walt Disney Company worth approximately $11.1 billion, and 38.5 million shares of Apple Inc. As of 2016, Powell Jobs and her family are ranked 44th in the Forbes' annual list of the world's billionaires. According to the same list, she is the richest woman in the Technology industry.

As of 2013, Powell Jobs sits on the board of Directors of College Track, NewSchools Venture Fund, Conservation International, and Stanford University. She is chair of the board of Directors of XQ and also sits on the chairman's advisory board of the Council on Foreign Relations. In 2014, she was ranked as the 29th most powerful woman in the world by Forbes. Her ranking rose from #39 in 2013.

In September 2015, Powell Jobs launched a $50 million project to create high schools with new approaches to education. Called XQ: The Super School Project, the initiative aims to inspire teams of educators, students, and community Leaders to create and implement new plans for high schools. Efforts include altering school schedules, curriculums and technologies in order to replace the country's century-old high school education model. Funding for XQ comes from Powell Jobs' Emerson Collective. Following an initial $50 million financial contribution, XQ announced an additional contribution, awarding ten schools $10 million each, for a total financial contribution of $100 million. The schools were chosen from approximately 700 submissions nationwide. Powell Jobs' team of advisors is led by Russlynn H. Ali.

On July 28, 2017, Powell Jobs organization Emerson Collective (based in Palo Alto, California) acquired majority ownership of The Atlantic.