Orangeburg County Sheriff Larry Williams said the boys, ages 1 and 2, were recovered from the North Edisto River after the car was found near a rural boat landing.
Their mother, whose name was not released, was being held Monday on a charge of leaving the scene of an accident, Williams said.
He said the Highway Patrol was notified about 6:15 a.m. Monday that there had been an accident and a woman needed help getting her children out of the car. Divers were brought to the scene.
The children, still strapped in their child seats, were dead when the car was lifted from the water about 45 minutes later, he said.
"Early in the investigation, the state patrol felt there was not enough indicators to substantiate that there was an automobile accident," Williams said. "We are looking into all possibilities as to what happened."
The woman, who did not have a cell phone, walked some distance down the country road by the boat landing and flagged down a passing motorist to call the Highway Patrol.
"She showed some emotion, but I can't say she was overly distraught," the sheriff said. "Through her statements, there are some things we think are not believable."
The sheriff said boat landing is down an asphalt road from the road that crosses the river and authorities are investigating how it could have been a traffic accident.
Williams said the children's father did not live with the family. The sheriff said authorities were attempting to contact him.
The county coroner did not immediately return a phone call from The Associated Press. Orangeburg is about 35 miles south of Columbia, the state capital.
The incident was reminiscent of the deaths of two other toddlers in South Carolina.
In 1994, in a case that made headlines worldwide, Susan Smith left her 3-year-old and 14-month-old sons strapped in their car seats as she rolled her car into a lake in Union County in the northwest part of the state.
She was convicted in their deaths and is serving a life prison term.