Court documents state that 53 migrants died in Texas heat from the truck driver.
Officials say that Homero Zamorano (45), was found in hiding near the truck Monday. He is one of the four people being charged.
Christian Martinez, the alleged conspirator of Mr Zamorano's murder, is accused of sending each other text messages before and after the truck was discovered.
This is the most horrific human trafficking incident in American history.
Children found in the car are still being treated at hospital. These victims came from Guatemala, Honduras and El Salvador.
He was discovered hiding in the bushes by Mr Zamorano. Mexican officials claim that he tried to pretend to be one of the survivors at first.
Surveillance photos of him driving the truck passed a US Border Patrol checkpoint at Laredo in Texas led to his arrest.
Federal court documents reveal that a confidential informant for Immigration and Customs Enforcement and Texas Police told officials that Mr Martinez and Mr Zamorano had spoken to each other after the deaths were reported.
Martinez claimed that Martinez said, "The driver did not know the air conditioner unit had stopped working. This was the reason the people died."
According to the documents, Mr Martinez and the informant were within a few metres of one another when the conversation occurred.
If found guilty of conspiracy and smuggling, both suspects could face the death penalty.
Juan Claudio D'Luna–Mendez, and Francisco D'Luna–Bilbao were also accused. They were charged with firearms possession as well as being illegally in the US. Both men are Mexican citizens.
27 Mexican citizens were among the victims, along with 14 Hondurans and seven Guatemalans, two Salvadorans, and fourteen Hondurans.
Mexican authorities claim that 67 migrants were in the lorry while San Antonio prosecutors have claimed 64.
Friday's announcement by the Bexar County Medical Examiner's Office stated that six of 53 victims had been identified as a result of Monday's incident.
Additionally, 42 "potential identifications” have been made. Five remain unidentified.
On Friday, also the Bexar County Sheriff's office started investigating an abandoned 18-wheel truck that was discovered in a residential area a few miles from the original vehicle.
Officials tell CBS News that 13 migrants were discovered in the latest truck.
"Preliminarily it appears that no individuals have sustained any major injuries," said the sheriff's department on Facebook. They also stated that they would release more information once they are available.
People-smuggling is a significant industry at the US-Mexico border.
A record number of undocumented migrants from Mexico were detained in May as they tried to enter the country illegally.
Recent reports have shown that mass deaths of this nature have been reported on numerous occasions all over the globe. The worst are:
