Under the agreement, migrants from El Salvador and Honduras who pass through Guatemala can be returned to the country to seek asylum there first.
But some Mexican migrants too could now face deportation, the US Department of Homeland Security announced.
Mexico rejected the plan, saying it could affect hundreds of people.
The controversial deal, reached last July, was part of President Donald Trump's efforts to stop people trying to reach the US through Mexico. Many say they are fleeing violence and poverty in El Salvador, Guatemala and Honduras.
At the time, critics said migrants would be at risk in Guatemala, where the murder rate is five times that of the US, according to the World Bank. Activists have also said the country does not have the resources to process and host large numbers of applicants.
Step into the shoes of a migrant
Migrants camped on border endure cold snap
Is there a crisis on the US-Mexico border?
"Certain Mexicans seeking humanitarian protections in the United States may now be eligible to be transferred to Guatemala and given the opportunity to seek protection there," a US Department of Homeland Security spokesperson said in a statement on Monday.
In theory, the expanded plan could see a Mexican being deported from El Paso in Texas, across the border from Ciudad Juárez, to Guatemala, some 2,500km (1,500 miles) away.
In a statement, Mexico's foreign ministry condemned the measure, saying some 900 asylum seekers could be affected from February. The government, it said, would closely monitor "human rights set out in the international agreements signed and ratified" by both countries.
Since the US began implementing the deal in November, 52 migrants have been sent to Guatemala, Alejandra Mena, a spokeswoman for the Guatemalan immigration institute told Reuters news agency. So far, only six have applied for asylum, she said.
Guatemalan President-elect Alejandro Giammattei, who takes office this month, told Reuters he would review the deal, signed by President Jimmy Morales after Mr Trump threatened to impose tariffs on his country. The US reached similar agreements with Honduras and El Salvador last year.