The win was Clinton's third victory in the first four Democratic contests, and solidified her status as the strong front-runner to capture the party's nomination for the Nov. 8 presidential election.
The former secretary of state's victory also established her strength among black voters, a crucial Democratic constituency who make up more than half of the party's primary electorate in South Carolina.
The result raised more questions about whether Sanders, the democratic socialist US senator from Vermont, will be able to expand his support beyond his base of predominantly white liberals.
Recognizing his steep odds in South Carolina, Sanders had spent most of the past week in states that will vote in March.
As the results rolled in on Saturday, he was scheduled to hold a rally in the 'Super Tuesday' state of Minnesota.
"Let me be clear on one thing tonight. This campaign is just beginning. We won a decisive victory in New Hampshire. She won a decisive victory in South Carolina. Now it's on to Super Tuesday," Sanders said in a statement.
The Democratic race now becomes a broader national contest.
Eleven states, including six in the South with large minority populations where polls show Clinton with big leads, will vote on Super Tuesday and four more over the next weekend.
Clinton's camp was hoping her apparent big win in South Carolina, after more narrow victories in Iowa and Nevada and Sanders' clear win in New Hampshire, would set her up for a big night on Tuesday, when about 875 delegates will be up for grabs, more than one-third of those needed to win the nomination.
