She has sought to set herself apart from the dozen or more Democrats vying to challenge President Donald Trump in next year's presidential election with a flurry of policy proposals at an early stage of the campaign.
Investors, however, shrugged off her comments with shares in the three companies barely affected.
Any such proposal would face myriad obstacles in Congress and the courts.
The senior United States senator and a leading candidate for the Democratic nomination said the companies had "bulldozed competition and tilted the playing field in their favour" as she laid out a plan for strict antitrust rules.
Warren says she would work to pass legislation to designate parts of these companies as what she calls "platform utilities" and force Amazon Marketplace, Google's ad business, and Google's search business to separate from their parent companies.
Facebook would have to split off WhatsApp and Instagram, and Google would have to unwind itself from Nest, Waze and DoubleClick. Amazon.com was down 1.4 percent.
Warren's big-tech breakup plan is one of the strongest initiatives introduced by any 2020 candidate.
Tech companies have come under increasing fire. Amazon has replaced brick and mortar stores and has been criticized for its poorly-paid warehouse workers. Under this proposal, Google would be forced to spin off its search business. Facebook declined to comment.
To deal with today's tech behemoth challenge, Warren suggests two major steps.
There have been increasing calls in the press, government, and legal worlds that our current tech giants constitute monopolies the likes of which we haven't seen since the Gilded Age, and that we need to give them the Gilded Age treatment. In late February, Warren announced a plan to guarantee every American free or affordable childcare. "In some cases, structural separation like Sen".
Amazon.com (ticker: AMZN) shares were down just over 1% in Friday trading, Facebook (FB) was off about 0.6%, and Alphabet (GOOGL), Google's parent, was nearly flat.
Warren made her political mark by going after big banks after the 2007-2009 financial crisis. She's also competing directly with Vermont Senator Bernie Sanders for the votes of the party's progressive wing, a key constituency in the months-long series of caucuses and primaries leading to the nomination.