Police have arrested a US couple who attempted to cross the border into Mexico with the body of two-year-old girl in a duffel bag.

Johnny Lewis Hartley, 39, and Mercy Mary Becerra, 43, were stopped by customs agents at the San Ysidro entry point on Tuesday.

Becerra fled and left Hartley with the duffel bag when stopped, according to Mexican authorities.

An x-ray of the bag revealed the body inside and further examination determined it was a two-year-old girl.

Investigators do not believe the pair are the girl's parents. Homicide detectives are yet to determine the cause of death.

Mexican authorities turned the pair over to US investigators, who interviewed and booked them into San Diego prisons.

Both were charged with one count of murder and child cruelty leading to death.

Henry Munoz, who lives in the same apartment building as the couple, said he was shocked they were accused of such a thing.

"It’s just really sad that someone could do that," Mr Munoz told CBS2 .

He said that the couple lived with a number of children: "Two twins, a couple of older ones. Four were in their teens."

They tried to enter Mexico through the San Ysidro entry point (pictured) on Tuesday, but were arrested by police (Image: AFP)