The new plants will be built over the next five years, and are expected to create more than 3,000 jobs for skilled workers like engineers and scientists as well as 10,000 construction jobs, the company said.
Lilly said it will announce the locations of the sites later this year.
The announcement comes less than a week after U.S. President Donald Trump met with chief executives from major drugmakers, including Lilly CEO David Ricks, to discuss industry concerns such as tariffs on drug imports.
U.S. Secretary of Commerce Howard Lutnick said at the press conference that Lilly was doing "exactly what the President was hoping would happen."
Ricks said he hoped the government would exempt medical supplies from potential tariffs and continue to pursue further tax reforms.
The CEO said in a statement earlier on Wednesday that tax-cutting legislation introduced in Trump's first term had been foundational to the drugmaker's domestic manufacturing investments.
Trump, who campaigned on a promise to boost domestic manufacturing, has been piling pressure on drugmakers since taking office to move medicine production to the U.S. He suggested last week that he could impose a 25% duty on pharmaceutical and other imports.
Other sectors are also making manufacturing announcements. Earlier this week, Apple (AAPL.O) said it would spend $500 billion in the U.S. over the next four years, but analysts said some of that included current commitments.
The U.S. and its major trading partners have agreed to reciprocal tariff elimination for pharmaceutical products and chemicals used in drug production for the past 30 years, according to the U.S. Trade Representative's office.
Despite telling Republicans in a White House meeting earlier this month that he was considering such an exemption, Reuters reported, Trump has yet to rule them out.
Ricks also said at the conference that he looked forward to working with the new administration to finalize a rule introduced by President Joe Biden last year that would require the Medicare and Medicaid government health programs to cover weight-loss drugs like Lilly's Zepbound.
Responding to a question about federal employee firings at the U.S. Food and Drug Administration, the CEO said Lilly's fees go toward funding staff at the agency and the company would be concerned if those funds "were directed towards something else."
Lilly, which has become the world's most valuable healthcare company worth more than $855 billion, said it has already committed $23 billion to boosting its U.S. manufacturing footprint since 2020. Its Wednesday announcement brings that total to more than $50 billion.
Three of Lilly's new plants will be used to manufacture pharmaceutical raw ingredients, while the fourth will make injectable medicines, the drugmaker said.
