A federal jury in Cleveland on Tuesday found that the companies owning CVS, Walgreens and Walmart pharmacies were liable for contributing to the opioid epidemic in two Ohio counties—the first, potentially influential verdict among many lawsuits targeting pharmacy chains.

In the suit, attorneys for Lake and Trumbull counties in northeastern Ohio had argued that the chains failed to stop pain pills from flooding the counties and false prescriptions from being filled. The counties argued that by enabling the opioid crisis the...

A federal jury in Cleveland on Tuesday found that the companies owning CVS, Walgreens and Walmart pharmacies were liable for contributing to the opioid epidemic in two Ohio counties—the first, potentially influential verdict among many lawsuits targeting pharmacy chains.

In the suit, attorneys for Lake and Trumbull counties in northeastern Ohio had argued that the chains failed to stop pain pills from flooding the counties and false prescriptions from being filled. The counties argued that by enabling the opioid crisis the pharmacy companies had created a public nuisance costing them each about $1 billion in law-enforcement, social-services and court expenses.

The companies argued that they had tried to stop pills from being illegally diverted and followed procedures required by federal and state regulators. They said that others were to blame in the crisis and that the counties had failed to show that the pharmacies played a major role in the epidemic.

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The verdict, delivered after a six-week trial, came in a so-called bellwether case that attorneys elsewhere have watched closely. Similar cases across the country continue to play out against pharmaceutical manufacturers and distributors, but Tuesday’s verdict was the first against deep-pocketed pharmacy chains.

Bellwether cases typically don’t carry precedential weight, but lawyers on similar cases across the country often use them as guideposts for settlement talks.

Although judges in opioid cases in Oklahoma and California recently issued judgments against plaintiffs’ public-nuisance claims in cases involving drugmakers, some legal experts said it was difficult to say whether the Ohio case could meet a similar fate on appeal. Public-nuisance laws vary by state, adding to the possibility of different results in different jurisdictions.

“The public-nuisance theory in general is pretty novel and untested as it applies to the sale of controlled substances,” said Elizabeth Burch, a University of Georgia law professor. “We’re so early in the overall distribution that we don’t know whether these are outliers or trendsetters.”

Lawyers for the plaintiffs hailed Tuesday’s verdict.

“For decades, pharmacy chains have watched as the pills flowing out of their doors cause harm and failed to take action as required by law,” they said in a joint statement. “Instead, these companies responded by opening up more locations, flooding communities with pills, and facilitating the flow of opioids into an illegal, secondary market.”

All three companies said they planned to appeal the verdict, arguing that Ohio’s public-nuisance law had been applied incorrectly in the case.

“‘The public-nuisance theory in general is pretty novel and untested as it applies to the sale of controlled substances.’”

— Elizabeth Burch, University of Georgia law professor

Michael DeAngelis, a spokesman for CVS Health Corp. , said the company strongly disagreed with the verdict. “Pharmacists fill legal prescriptions written by DEA-licensed doctors who prescribe legal, FDA-approved substances to treat actual patients in need,” he said, referring to the Drug Enforcement Administration and the Food and Drug Administration.

Walmart Inc. said in a statement that the “plaintiffs’ attorneys sued Walmart in search of deep pockets while ignoring the real causes of the opioid crisis—such as pill mill doctors, illegal drugs, and regulators asleep at the switch.”

A spokesman for

Walgreens Boots Alliance Inc. said the court erred in allowing the case to go before a jury.

Shares of the three companies, which operate thousands of pharmacies across the country, were little changed by Tuesday’s close.

The jury only assessed liability in the case. U.S. District Judge Dan Polster,

who oversaw the trial, will determine how much the companies must pay to address the public nuisance created in the two counties. In a press conference after the verdict, plaintiffs’ attorneys said they would seek damages of $1.1 billion and $1.3 billion, respectively, for the two counties.

Judge Polster has consolidated lawsuits that more than 3,000 communities have filed against drug manufacturers, distributors and pharmacies and has chosen some cases as bellwethers.

Lawyers for the counties had argued that the pharmacies were the last line of defense against addiction spreading in the communities. Defense attorneys had countered by saying that the companies had tried to stop pills from being illegally diverted and that others were to blame for the crisis.

Two other chains, Rite Aid and Giant Eagle, have reached previous settlements with the two counties, terms of which haven’t been disclosed. The companies had denied wrongdoing in court documents.

More than 80 million opioid pills were shipped to Trumbull County, with a population of less than 200,000, from 2006 to 2012, according to government data. More than 60 million opioid pills were shipped to Lake County, with a population of about 230,000, over that period.

The opioid crisis has triggered lawsuits by states, local governments, Native American tribes, hospital groups and others against players in the pharmaceutical industry. The lawsuits allege that drugmakers pushed their painkillers for uses far beyond what was medically necessary and that distributors and pharmacies didn’t do enough to halt masses of pills from flowing into communities.

In July, states unveiled a $26 billion settlement with drug companies to resolve thousands of opioid lawsuits. The nation’s three largest drug distributors— McKesson Corp. , AmerisourceBergen Corp. and Cardinal Health Inc. —and the drugmaker Johnson & Johnson negotiated the deal for more than two years.

Plaintiffs in several cases have hit headwinds recently. Earlier this month the Oklahoma Supreme Court overturned a $465 million opioid-related judgment against Johnson & Johnson. The court found that the state’s public-nuisance law didn’t apply to “manufacturing, marketing and the selling of prescription opioids.” Also this month a California judge cleared drugmakers of liability in a case alleging that they had caused the state’s opioid crisis.

A ruling is pending in a separate case in West Virginia in which a county and city accuse drug distributors of fueling the opioid epidemic there.

Opioids were involved in more than 70% of the nearly 841,000 U.S. drug overdose deaths since 1999, according to data from the Centers for Disease Control and Prevention. More than 100,000 fatal overdoses occurred in the 12-month period ended in April, with three-quarters involving opioids and driven largely by fentanyl, CDC data show.

Write to Kris Maher at kris.maher@wsj.com