Drug overdoses killed about 72,000 Americans last year, a record number that reflects a rise of around 10 percent, according to new preliminary estimates from the Centers for Disease Control. The death toll is higher than the peak yearly death totals from H.I.V., car crashes or gun deaths.

Analysts pointed to two major reasons for the increase: A growing number of Americans are using opioids, and drugs are becoming more deadly. It is the second factor that most likely explains the bulk of the increased number of overdoses last year.

The picture is not equally bleak everywhere. In parts of New England, where a more dangerous drug supply arrived early, the number of overdoses has begun to fall. That was the case in Massachusetts, Vermont, and Rhode Island; each state has had major public health campaigns and has increased addiction treatment. Preliminary 2018 numbers from Massachusetts suggest that the death rate there may be continuing to fall.

But nationwide, the crisis worsened in the first year of the Trump presidency, a continuation of a long-term trend. During 2017, the president declared the opioid crisis a national public health emergency, and states began tapping a $1 billion grant program to help fight the problem.

“Because it’s a drug epidemic as opposed to an infectious disease epidemic like Zika, the response is slower,” said Dan Ciccarone, a professor of family and community medicine at the University of California, San Francisco, who studies heroin markets. “Because of the forces of stigma, the population is reluctant to seek care. I wouldn’t expect a rapid downturn; I would expect a slow, smooth downturn.”

A large government telephone survey suggests that around 2.1 million Americans had opioid use disorders in 2016, but that number may be an undercount because not all drug users have telephones and some may not mention their drug use because of the stigma. Dr. Ciccarone said the real number could be as high as four million.

The number of opioid users has been going up “in most places, but not at this exponential rate,” said Brandon Marshall, an associate professor of epidemiology at the Brown University School of Public Health. “The dominant factor is the changing drug supply.”

Strong synthetic opioids like fentanyl and its analogs have become mixed into black-market supplies of heroin, cocaine, methamphetamine and the class of anti-anxiety medicines known as benzodiazepines. Unlike heroin, which is derived from poppy plants, fentanyl can be manufactured in a laboratory, and it is often easier to transport because it is more concentrated.

Unexpected combinations of those drugs can overwhelm even experienced drug users. In some places, the type of synthetic drugs mixed into heroin changes often, increasing the risk for users. While the opioid epidemic was originally concentrated in rural, white populations, the death toll is becoming more widespread. The penetration of fentanyl into more heroin markets may explain recent increases in overdose deaths among older, urban black Americans; those who used heroin before the recent changes to the drug supply might be unprepared for the strength of the new mixtures.

“Even when you think you’re doing better, all it takes is one bad batch of fentanyl in any state and you’re going to have deaths,” said Mark Levine, a physician and the health commissioner of Vermont, which has made major investments in addiction treatment but still experienced a spike in deaths in 2016. Last year, deaths fell slightly there.

According to the C.D.C. estimates, overdose deaths involving synthetic opioids rose sharply, while deaths from heroin, prescription opioid pills and methadone fell.

In much of the West, overdose deaths have been flatter as the epidemic has raged in parts of the East and Midwest. That geographical pattern may be a result of the drug supply. Heroin sold west of the Mississippi tends to be processed into a form known as black tar that is difficult to mix with synthetic drugs. The heroin sold toward the east is a more processed white powder that is more easily combined with fentanyl.

Overdose deaths rose sharply in several mid-Atlantic and Midwestern states. In Ohio, Indiana and West Virginia, where the opioid death rate has been high for years, overdose deaths increased by more than 17 percent in each state. In New Jersey, they rose 27 percent.

The C.D.C. numbers for 2017 are an estimate, not a final count. The federal government collects death records from states throughout the year. But some deaths can take longer to investigate than others. The C.D.C. adjusts early numbers based on the number of deaths still under investigation by assuming a predictable proportion of them will turn out to be drug overdoses based on past experience. Using deaths that are confirmed, the agency measured a 10.2 percent increase in overdose deaths between 2016 and 2017. Using its adjusted data, the increase was 9.5 percent.

There are reasons for optimism that the recent increases in overdose deaths will not continue. The monthly C.D.C. numbers suggest that deaths might have begun leveling off by the end of the year. Continuing funding may help more states develop the kind of public health programs that appear to have helped in New England.

“There’s a lot of money going into the system, and it takes some time for this to translate into new infrastructure,” said Chris Jones, the director of the national mental health and substance use policy laboratory. “That’s particularly true for places where it wasn’t already there.”

In Dayton, Ohio, a hot spot for the epidemic, public health officials are seeing signs of progress. After instituting a new emergency response strategy — and drawing from new federal and state grant funds — the county health department has documented reductions in overdose deaths, emergency room visits and ambulance calls of more than 60 percent between January 2017 and June of this year.

The county has reduced medical opioid prescribing; increased addiction treatment resources; expanded community access to an anti-overdose drug called naloxone; and provided addiction treatment to prisoners in its county jail, among other measures.

Barbara Marsh, the assistant to the Dayton and Montgomery County health commissioner, says she hopes the trend will hold and provide some lessons for other parts of the state. “It’s definitely wait and see,” she said. “We want to continue seeing a decline.”

Congress is debating a variety of bills to fight the epidemic. Many of the measures, which have passed the House but have not reached the Senate floor, are focused on reducing medical prescriptions of opioids and are meant to reduce the number of new drug users. But the package also includes measures that could expand treatment for people who already use opioids.

The epidemic could also intensify again. One worrying sign: Dr. Jones said there is some early evidence that drug distributors are finding ways to mix fentanyl with black tar heroin, which could increase death rates in the West. If that becomes more widespread, the overdose rates in the West could explode as they have in parts of the East.