A total of 11 human plague cases have been recorded by the US health authorities since April, with three of them fatal.
"It is unclear why the number of cases in 2015 is higher than usual," the US Centers for Disease Control and Prevention said.
The CDC said that having 11 cases in just the past four months is unusual.
"During 2001 to 2012, the annual number of human plague cases reported in the United States ranged from one to 17," the agency said in a statement.
The median number of annual plague cases across the past decade has been three.
Plague is a rare and dangerous disease that is caused by a bacterium, known as Yersinia pestis, that circulates in wild rodents and their fleas.
People can get the plague if they are bitten by an infected flea, or if they come in close contact with an infected person or animal, including cats and dogs, health authorities said.
This year's cases originated in the western United States, with four cases in Colorado and two each in Arizona, New Mexico and California. Another infection took place in Oregon.
One of the California infections was of a resident of the southeastern state of Georgia, who later returned to their home state.
"The two cases in Georgia and California residents have been linked to exposures at or near Yosemite National Park in the southern Sierra Nevada Mountains of California," the CDC said.
Three patients contracting the plague have died -- aged 16, 52 and 79 -- and nine of the 11 infected have been males.
The CDC urged doctors to consider a diagnosis of plague if they see patients with fever, abdominal pain, nausea and vomiting, especially if they have recently visited the western United States or are residents of the region.
People who spend time outdoors in areas where plague is endemic "should wear long pants when possible and use insect repellent on clothing and skin," as well as "avoid direct contact with ill or dead animals and never feed squirrels, chipmunks, or other rodents."
Bubonic plague is the most common type of plague and accounts for 80 percent of cases today. It is also the form of plague known as the Black Death because it killed 50 million people in Europe in the 14th century.
Death rates from the plague used to reach as high as 93 percent, but in the modern era antibiotics have lowered the fatality rate to around 16 percent, the CDC said.
Last month, a girl from the Los Angeles area who visited Yosemite in mid-July tested positive for the plague, but was treated and has since recovered.
Some campgrounds in the national park, the US's third-most visited, have been temporarily closed and fumigated after several dead squirrels were found to be carrying the plague.