Hackers stole cryptocurrencies worth more than $600 million from Poly Network, a decentralized finance, or DeFi, platform, in one of the largest crypto heists of recent years.

Poly Network, which uses digital assets for lending and other financial transactions, disclosed the hack in a series of Twitter posts Tuesday. Blockchain security company SlowMist estimated that the stolen cryptocurrencies were worth over $610 million at the time.

The hackers made away with digital currencies including ether and tokens backed by bitcoin, as well as tether, a coin designed to mimic the value of the U.S. dollar, and the Shiba Inu coin, a novelty spinoff of the joke cryptocurrency dogecoin inspired by the Shiba Inu breed of dog.

“The amount of money you hacked is the biggest one in defi history. Law enforcement in any country will regard this as a major economic crime and you will be pursued,” Poly Network wrote in a letter posted on Twitter.

The Poly Network hack is on par in size with infamous breaches at Coincheck in 2018 and Mt. Gox in 2014, where digital assets valued at around $550 million and $400 million, respectively, went missing. The incident highlights the risks of trading in the unregulated market, where theft, fraud and scams are common.

Poly Network pleaded with the hackers to return the money. “It is very unwise for you to do any further transactions. You should talk to us to work out a solution,” the letter said.

Around $5 million of the stolen cryptocurrencies began trickling back to Poly Network Wednesday, the company said.

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Poly Network is one in a burgeoning DeFi sector, which includes companies that offer financial services on public blockchains, the digital ledgers that underpin cryptocurrencies. Similar to regular banks, DeFi outfits lend out assets and write derivative contracts, among other services. Investors often use DeFi services to borrow against their crypto holdings and amplify their bets.

A big difference with mainstream financial institutions is that everything revolves around the use of privately generated digital currencies rather than ones issued by governments. There is no central bank through which transactions are processed and limited oversight or regulation.

The Poly Network hack rippled to other platforms. Paolo Ardoino, chief technology officer of Tether, tweeted that his company froze $33 million of its cryptocurrency in one of the hackers’ addresses.

Changpeng Zhao, chief executive of Binance, the largest cryptocurrency exchange in the world, tweeted, “We are coordinating with all our security partners to proactively help.”

The breach of Poly Network didn’t appear to hit the value of the coins that were stolen. Ether, the second most used cryptocurrency after bitcoin, traded around $3,218 on Wednesday, up 2.1% from its level at 5 p.m. ET on Tuesday. The Shiba Inu coin was little changed as well, according to CoinMarketCap.

The hacker was able to access the assets by exploiting a vulnerability between “contract calls,” according to Poly Network.

Aby Huang, chief executive of security company SlowMist, said this means the hackers found vulnerabilities when two programs that automatically execute transactions on the blockchain were running at the same time.

Because blockchain transactions are recorded on a public ledger, Poly Network and others seeking to recoup the money may be able to gather clues about where the money is headed.

“Every transaction they make will cause an extra piece of evidence for investigators to look into,” said Jake Moore, a specialist at ESET, a cybersecurity company.

Write to Anna Hirtenstein at anna.hirtenstein@wsj.com