San Diego developer Moe Ebrahimi paid $720,000 late last year for a site where he planned to build apartments. He expected to own it for years, believing the Logan Heights neighborhood would gentrify.

That all changed earlier this year, when Mr. Ebrahimi put the land up for sale with an asking price of $1 million.

The developer shifted tactics after learning that anyone buying his property would be eligible for lucrative tax benefits. That’s because his land resides in one of the nearly 9,000 so-called “opportunity zones” across the U.S. intended to stoke economic development in low-income areas.

“My friends and I were high-fiving,” he said. “This was a jackpot.”

Tens of thousands of other U.S. property owners like Mr. Ebrahimi stand to benefit from a section of last year’s Republican tax overhaul. For months, these tax provisions received little public attention but they have become a focus of the real-estate industry.

Anyone who makes a qualified investment in an opportunity zone can defer capital-gains from an unrelated investment, whether it’s from the sale of other real estate or cashing out a big gain on a tech stock. What’s more, any gains realized on a zone investment are tax-exempt if they are held for at least 10 years.

The Treasury Department last week proposed long-awaited guidelines that give investors enough certainty to begin the process. Billions of dollars have started piling into new real-estate funds targeting opportunity zones. Now that the government has clarified the rules, these fund managers are poised to begin collecting money and investing.

But even before Treasury’s announcement, sales activity had already picked up in opportunity zones throughout the country. Eager investors studied maps and bought property, anticipating that prices would rise when the new funds put the money to work.

Fund managers have been focusing primarily on sites that are ripe for new construction or properties that are fixer-uppers. Opportunity-zone real-estate investments have to be one or the other to qualify for the tax breaks.

Sales of development sites in opportunity zones nationwide have spiked 80% in the first three quarters of 2018, compared with the same period last year, according to data firm Real Capital Analytics. Meanwhile, owners have marked up asking prices for land or properties in some zones by more than 50%, market participants say.

This has been especially true in parts of Oakland, San Diego, Phoenix, Atlanta, Portland, Ore., and other growing cities where real-estate speculation had been stirring even before the program started.

In cities that have opportunity zones and are on Amazon.com Inc.’s shortlist as potential sites for its second headquarters—like Newark, N.J., and Pittsburgh—speculators have had twice the incentive to buy.

“The enormity of capital the opportunity funds could channel into these limited and defined geographic areas could really be profound,” said Robert White Jr., the founder of data provider Real Capital, in an email. “It is like 1031 on steroids,” he said, referring to the 1031 tax break, which until now has been one of the most popular among commercial-property investors.

A 1031 exchange enables sellers of real estate and other assets to defer capital-gains taxes by reinvesting the proceeds in “like-kind” properties.

Not all zones are attracting investor attention. Many are in remote, rural areas or are suffering from long-term problems that can’t be simply overcome with tax incentives.

Officials in many states who helped designate zone locations say they were careful to focus on neighborhoods that needed the most help, ones with high unemployment and low median incomes. Their intention wasn’t to steer more capital toward neighborhoods already on the rise.

“An investment like this could be the thing that pushes a neighborhood over the edge towards gentrification,” said David Reifman, commissioner of the Chicago Planning and Development Department. “That’s not what we’re trying to do.”

Still, investors clearly view some zones as more primed for growth than others. In the Bronx, for example, investors purchased $225.7 million worth of development sites in zones in the first nine months of this year, up from $24 million during the same period in 2017, according to Real Capital.

In Salt Lake City, deal activity increased to $160 million this year, up from $21.4 million in 2017. During that same period in Salt Lake City, sales of development sites in non-zones declined to $40.5 million this year from $53.8 million in 2017, Real Capital said.

The increased demand is pushing up asking prices. In Portland, owners of development sites in zones are asking as much as 50% more than two years ago, brokers say.

Many brokerages are now citing the zones in marketing materials. For example, Real Estate Investment Group, of Portland, is listing a 2.8-acre waterfront development site in the city’s Pearl District. The first page of the brochure points out that it is “inside the opportunity zone” in all-capital letters.

“The opportunity zone is definitely the talk of the town,” said George Diamond, one of the firm’s founders.

Write to Peter Grant at peter.grant@wsj.com