Harvard, the richest university in the United States, said it would seek to raise US$6.5 billion in donations to fund new academic initiatives and bolster its financial aid programme.
The fundraising drive by the Cambridge, Massachusetts, institution is the university's biggest and believed to be the most ambitious ever undertaken by a university, ahead of one concluded last year by Stanford University in California that raised US$6.2 billion.
Harvard President Drew Gilpin Faust said the campaign would help the school meet the world's increasingly complex and pressing needs.
"We will meet these challenges, and in doing so, we will reaffirm what makes Harvard - and universities in general - such essential and irreplaceable contributors to the pursuit of knowledge and the welfare of the world," Faust said in a press release.
Harvard unveiled its campaign at an event featuring Bill Gates, who spent three years at the school in the 1970s before dropping out to co-found Microsoft.
Gates, who was ranked by Forbes magazine this year as the world's second-richest person behind Mexico's Carlos Slim, joked about his decision to leave the university during a talk before alumni and donors.
"You never say that you are 'dropping out' of Harvard. I 'went on leave' from Harvard," he said. "If things hadn't worked out for my company, Microsoft, I could have come back."
The university has already raised US$2.8 billion from more than 90,000 donors during the pre-launch phase of the campaign, its first major fundraising drive in more than a decade, it said.
Harvard's investment portfolio is worth about US$30.7 billion, roughly the size of the annual gross domestic product of the Baltic nation of Latvia. That endowment shrank 0.05 per cent in the fiscal year ended in 2012, after double-digit gains the previous year, according to the most recent figures from the university.
"The endowment is meant to last forever. ... It enables our faculty to do groundbreaking research and supports financial aid for our students," Vice President for Alumni Affairs & Development Tamara Rogers said. "In order to undertake new activities, we are going to have to raise new funds."
Asked why people would give to an already wealthy school such as Harvard and not some other cause, Harvard Provost Alan Garber said the school has a history of helping solve the world's problems, and donors believe "Harvard can do uniquely well".
"This ranges from educational innovation to scientific breakthroughs that have changed the world," he said.
Nearly half of the money raised in the new campaign will support teaching and research, while a quarter will go for financial aid and related programmes. The rest will go towards capital improvements and a flexible fund, according to Harvard, recently ranked America's No 2 university behind Princeton by US News & World Report.
Four years ago, Harvard was forced to suspend its campus expansion and put the construction of a US$1 billion science complex on hold after its endowment lost 27.3 per cent during the financial crisis.
Funds from the campaign will help finance that project in Boston . Construction resumed a year ago.
Additional reporting by Associated Press