The 31 year old, who has two children with Guzman, was arrested at Dulles International Airport and will appear in court in Washington DC on Thursday.
A guilty plea could see her sentence reduced.
Her husband was the leader of the Sinaloa Cartel, which the US Justice Department describes as “one of the world’s most prolific, violent and powerful drug cartels,” and moved billions of dollars worth of drugs across the US-Mexico border over the course of four decades.
After years on the run and one successful escape from prison in Mexico, he was captured, extradited to the United States and was sentenced to life in prison in 2019.
Guzman is locked up in the highest-security prison in the United States, the ADX federal prison in Florence, Colorado.
There has been speculation that Ms Coronel is willing to turn on her husband in order to ensure a lighter sentence.
Ms Coronel appeared in court nearly every day of his three-month trial in New York and has boosted her own profile by appearing on reality television and launching a clothing range.
The Justice Department claims she took part in cartel activities and also allegedly assisted in two plots to help Guzman escape from Mexican prison, including the successful first one in 2015.
Ms Coronel met Guzman when she was a young beauty queen, and married him in 2007 when she was 18. The couple went on to have twin daughters, who were born in Los Angeles.
“I will follow to wherever he is (sic),” she told the Los Angeles Times of her husband in a 2017 profile. “I am in love with him. He is the father of my children.”
Mike Vigil, the Drug Enforcement Administration’s former chief of international operations, says she has good reason to cooperate.
“She has a huge motivation, and that is her twins,” Mr Vigil said.
The New York Times reported that in an agreement with the government Ms Coronel could be designated as a “minimal participant” in the conspiracy and is likely to be sentenced to far less time than would be expected for a crime of this nature.