WASHINGTON — Deaths from drug overdoses continued rising to record-breaking levels in 2021, nearing 108,000, according to preliminary new data published on Wednesday by the Centers for Disease Control and Prevention.

The increase of nearly 15 percent followed a much steeper rise of almost 30 percent in 2020, an unrelenting crisis that has consumed federal and state drug policy officials. The number of drug overdose deaths has increased every year but 2018 since the 1970s.

A growing share of deaths came from overdoses involving fentanyl, a class of potent synthetic opioids that are often mixed with other drugs, and methamphetamine, a synthetic stimulant. State health officials battling an influx of both drugs said many of the deaths appeared to be the result of combining the two.

Drug overdoses, which long ago surged above the country’s peak deaths from AIDS, car crashes and guns, killed about a quarter as many Americans last year as Covid-19.

Deaths involving synthetic opioids — largely fentanyl — rose to 71,000 from 58,000, while those associated with stimulants like methamphetamine, which has grown cheaper and more lethal in recent years, increased to 33,000 from 25,000. Because fentanyl is a white powder, it can be easily combined with other drugs, including opioids like heroin, and stimulants like meth and cocaine, and can be stamped into counterfeit pills for anti-anxiety drugs like Xanax. Such mixtures can prove lethal if drug users are unaware they are using fentanyl or are unsure of the dose.

Deaths from both classes of drugs have been rising in recent years.

But there is growing evidence that mixing stimulants and opioids — into combinations known as “speedballs” and “goofballs” — is growing more common, too. Dan Ciccarone, a professor of family and community medicine at the University of California, San Francisco, who studies drug markets, has just begun a multiyear study of the combination of opioids and meth.

“There’s an intertwined synthetics epidemic the likes of which we’ve never seen,” he said. “We’ve never seen a powerful opioid such as fentanyl being mixed with such a potent methamphetamine.”

The numbers released Wednesday are considered provisional, and may change as the government reviews more death records. But they added more definition to a crisis that has escalated sharply during the pandemic.

The White House in recent weeks announced President Biden’s first national drug control strategy, and a plan to combat meth use, unveiled last week by his drug czar, Dr. Rahul Gupta, the first medical doctor to oversee the White House Office of National Drug Control Policy. Overdose deaths involving meth almost tripled between 2015 and 2019 in people 18 to 64, according to the National Institutes of Health.

Mr. Biden is the first president to embrace harm reduction, an approach that has been criticized by some as enabling drug users, but praised by addiction experts as a way to keep drug users alive while providing access to treatment and support.

Instead of pushing abstinence, the approach aims to lower the risk of dying or acquiring infectious diseases by offering sterile equipment — through needle exchanges, for example — or tools to check drugs for the presence of fentanyl. Strips that can detect fentanyl have become increasingly valuable resources for local health officials, and some states have moved recently to decriminalize them, even as others resist.

The causes of the continued increase in overdoses are complex and hard to untangle, experts said. But state health officials and some addiction experts said the spike in overdoses, which began before the pandemic, could not be blamed solely on the disruptions that came with it, or on a major increase in the number of Americans using drugs.

Social isolation and economic dislocation, which have been widespread during the pandemic, do tend to cause relapses in drug use, and could have contributed to rising overdoses. Shutdowns early in 2020 also caused some addiction treatment providers to temporarily close their doors. But the pandemic alone does not explain the recent trend.

Policy changes made during the pandemic may have helped prevent more deaths. Regina LaBelle, an addiction policy expert at Georgetown University, said that early research has found that loosening rules to permit take-home methadone treatment had been beneficial, along with an increase in treatment via telemedicine.

“The difference in what we’re seeing now is not how many people are using,” said Dr. Anne Zink, the chief health official in Alaska, which saw the largest overdose death percentage increase of any state in the nation, according to the data released on Wednesday.

Instead, she said, the fentanyl supply had skyrocketed, in shipments that were difficult to track, penetrating even the most isolated parts of the state. Of the 140 fentanyl overdose deaths the state recorded in 2021, over 60 percent also involved meth, and nearly 30 percent involved heroin.

Fentanyl, which is made in a lab, can be cheaper and easier to produce and distribute than heroin, enhancing its appeal to dealers and traffickers. But because it is strong and sold in varying formulations, small differences in quantity can mean the difference between a drug user’s usual dose and one that proves deadly. It is particularly dangerous when it is used unwittingly by drug users who do not usually take opioids. The spread of fentanyl into a ever-growing portion of the nation’s drug supply has continued to flummox even states with strong addiction-treatment services.

Often synthesized in Mexico from precursor chemicals made in China, fentanyl long ago permeated the heroin markets of the Northeast and Midwest. But recent data shows it has established a strong hold in the South and West as well.

“The economics of fentanyl have just been pushing the other drugs out of the market,” said Dr. Joshua Sharfstein, a vice dean of the Bloomberg School of Public Health at Johns Hopkins University. “It’s just so cheap to buy fentanyl and turn around and put it in whatever.”

A recent study of illicit pills seized by drug enforcement authorities found that a substantial share of what is marketed as OxyContin, Xanax or the attention deficit hyperactivity disorder drug Adderall now contains fentanyl. The spread of these counterfeit pills may explain a recent sharp increase in overdose deaths among teenagers, who are less likely to inject drugs than older people.

Pat Allen, the Oregon Health Authority director, said that, as was the case in other states with surging overdose deaths, the clear difference in 2021 had been the ubiquity of fentanyl. Children as young as 12 are considered at high risk of obtaining counterfeit pills containing fentanyl, and high schoolers are overdosing on them, believing they are opioid painkillers or anti-anxiety medication. The state was working to send naloxone tool kits to schools, similar to a program it has used in fast food restaurants, where people were overdosing in bathrooms.

Mr. Allen said he had seen an alarming phenomenon among those who overdose: They perceive the risk of fentanyl to be low, even though the actual risk is “gravely higher.”

“We’ve had an addiction issue in Oregon which we’ve known about for a long time,” he said. “This takes that existing addiction issue and makes it much more dangerous.”

In 2021, overdoses amounted to one of the leading causes of death in the United States, similar to the number of people who died from diabetes and Alzheimer’s disease, and roughly a quarter of the number of people who died from Covid-19, the third leading cause of death, according to the C.D.C.

In Vermont, 93 percent of opioid deaths in 2021 were fentanyl-related, according to Kelly Dougherty, the state’s deputy health commissioner.

“In the beginning stages of the pandemic, we were attributing the increase to life being disrupted,” she said. But now, she added, a different explanation seems clear: “What is really the primary driver is the presence of fentanyl in the drug supply.”

The state’s celebrated “hub and spoke” model of addiction treatment and its aggressive use of medication-assisted treatment programs, she said, were not enough to contend with the ease and speed with which people overdose on fentanyl.

“You can have the most robust treatment system,” she said, “and not everybody is going to avail themselves of it when maybe they should, or before they end up overdosing.”

And fentanyl is showing up in counterfeit pills, Ms. Dougherty said, including in OxyContin.

She said Vermont officials had taken up new public messaging regarding fentanyl.

“Just assume that it’s everywhere,” she said.