READING, Pa.—This coal and steel region was thriving when Gary Martin started working construction sites in the mid-1970s. Ironworkers jammed the local union hall, the union sponsored a big picnic each spring, and business groups were flush with volunteers for charity drives.

Mr. Martin’s extended family attended church, as it had for generations, in an area called Irish Valley in neighboring Schuylkill County. Two-parent families were the norm, and fatal drug overdoses were so rare that some county coroners didn’t bother...