With 87 percent of the expected vote in, Clinton leads with 57 percent of the vote compared to Sanders' 43 percent.
The state's pledged 247 delegates will be awarded proportionally. There are an additional 44 superdelegates also up for grabs.
In her acceptance speech, Clinton said tonight's win was deeply personal.
"Today you proved, once again, there's no place like home," she said.
"In this campaign, we've won in every region of the country, from the north to the south to the east to west, but this one's personal. New Yorkers, you've always had my back and I've always tried to have yours," she added.
Clinton's win was largely expected by political insiders.
The former secretary of state, who represented New York in the Senate for eight years, had been leading all New York state polls by double digits in the week prior to the primary.
ABC News' MaryAlice Parks and Matthew Claiborne contributed to this report.