Smith initially reported to police, on October 25, 1994, that she had been carjacked by a black man who drove away with her sons still in the car. Smith made tearfull pleas on television for the rescue and return of her children. A Usenet chain letter circulated in the following days, asking Internet users to be on the lookout for the vehicle. However, nine days later, following an intensive, heavily publicized investigation and a nationwide search, Smith eventually confessed to letting her 1990 Mazda Protegé roll into nearby John D. Long Lake, drowning her children inside. ()

Many people across the United States and around the world, to whom she and her two "missing" sons had been the subject of an outpouring of sympathy, felt deeply betrayed. Their reaction to the betrayal was further aggravated by the fact that she had attempted to cast blame, falsely, upon a black man, making the case racially sensitive. Additionally, her alleged motive for the deaths — to dispose of her children so that she might have a relationship with a wealthy local man who had no interest in a "ready-made" family — was met with widely held contempt and revulsion. There has been no answer from Susan Smith regarding her choice not to give her estranged husband David Smith custody of the children, instead of killing them.

It later emerged that investigators had been suspicious of Smith's story from the beginning and believed she had actually killed her own children. From the second day of the investigation the authorities suspected that Smith knew where the children were. It was their hope that the children were still alive. Lakes and ponds began being searched, even the lake in which the children were eventually found. The reason for not finding the children earlier is because the authorities only thought the car could have traveled out about thirty feet and that was the extent of the search. Later they found out that the car was about sixty feet out; this was because of the speed the car had when it entered the lake and it drifted out on top of the water for about thirty feet. She'd taken a polygraph along with David two days after the boys disappeared. The results were inconclusive, but showed that she was lying when she said she didn't know where the boys were. She was polygraphed during every subsequent interview with investigators, and failed that question each time. There were also no other cars near the intersection where Smith said the carjacking had occurred. A big break in the case had to do with Smith's story on where she was carjacked. The particular red light at which she said she stopped is only triggered when a car is coming from the opposite direction. According to her, there were no other cars around so there would be no reason for her to stop at this intersection.

It was disclosed in her trial that Smith was molested in her teens by her stepfather Beverly Russell, an outwardly righteous pillar of the community, and a member of the South Carolina Republican party executive committee. Russell admitted that he molested Smith when she was a teenager and had consensual sex with her as an adult. Her biological father committed suicide when she was young and she very rarely had a stable home life.

While she has been in prison, two guards have been punished for having sex with Smith. Because of this she was moved to a prison in Greenwood where she is currently held, and in 2003 she placed a personal ad at WriteAPrisoner.com which has since been retracted.

• The 1995 episode of Law & Order entitled "Angel" was based on the Susan Smith case. The Smith case is referred to specifically in both the investigation and the eventual trial. The case is also referenced by a potential juror in the 14th season Law & Order episode "Gaijin".

• The song "Car Seat (God's Presents)" by Blind Melon, on the Soup album, is about the Susan Smith murders.

• The character Shirley Bellinger from the HBO drama Oz, who was executed for drowning her daughter by driving into a lake, is based on Smith.

• Canadian singer-songwriter Hayden's "When This Is Over" (from Everything I Long For, 1995) describes the tragedy from the perspective of Michael Smith.

• The first section of Cornelius Eady's Brutal Imagination (New York: Penguin Putnam Inc., 2001) recounts the murders in poetic verse from the perspective of the imagined black kidnapper.

• Poet Lee Ann Brown's The Ballad of Susan Smith is a sung poem set to an old southern mountain hymn tune. A music video of this poem can be found at Youtube.

• Susan Smith's story loosely inspired Richard Price's 1998 novel Freedomland, which was adapted to the 2006 film Freedomland starring Samuel L. Jackson and Julianne Moore.

• The Susan Smith case is referred to in the third season opener of the sitcom Arrested Development. In the episode, Lucille Bluth, freshly off her antidepressants in a flashback, cheers upon hearing the news of Smith's action. At the end of the episode, Lucille accidentally lets her car roll into a lake with her son Buster sleeping inside.

• In "The Calusari", an episode of The X-Files, parents are suspected in the death of a child, and the father says he and his wife are not like the woman who drowned her kids in a lake.

• Caroline Herring's song "Paper Gown" off her album Lantana is about Susan Smith and her crime.

• In the season 5 episode of South Park Butters' Very Own Episode, Butters' mom tries to kill her son by placing him in her car, letting it roll into a lake, and blaming it on "some Puerto Rican guy" (Butters later escapes the car unharmed.)

• On Lie to Me, a clip of Smith speaking to the press was shown to display, that while she sounded sincere about a car jacker taking her car, her face showed she was lying. Described as having as much emotion as if she was reading a grocery list.
• The Opie and Anthony Radio show make many references to the murder.

• The second episode of Glee makes reference to Smith, when Kendra says that Terri's craft room is "the only thing keeping her from 'going all Susan Smith' on that little angel."

• The History Channel used a video of Smith and her husband at a press conference where she is asking the public to help her find her children. The video was used in a segment on body language on the History Channel, Smith's body language displayed that she was faking her sadness and urgency when she asked the public to help her "find her missing children."

• She was also featured as a case study in an episode of Deadly Women.

• Her picture appears on the opening mugshots sequence of Criminal Minds