Williams was found dead at 6:15 p.m. Thursday in an El Segundo hotel room, Los Angeles County coroner's Capt. John Kades (KAY'-dihs) said.
An autopsy will determine the cause of death. A toxicology examination will take six weeks to be completed, Kades said.
Born Mary Vesta Williams on Dec. 1, 1957, to a disc jockey in Coshocton, Ohio, she had hits with "Once Bitten Twice Shy," "Sweet, Sweet Love" and the torch song "Congratulations," where she emotionally bids goodbye to her ex, about to marry someone else, on his wedding day.
Williams also appeared in movies and on television.
She was a saloon singer in the Mario Van Peebles movie "Posse" and she had a recurring role on the television situation comedy "Sister, Sister," playing actress Jackee Harry's best friend Monica.
Harry tweeted her condolences: "...just received truly devastating news: R&B great, and my friend of many yrs, Vesta Williams ((at)vesta4u), has passed away. (hash)RIPVesta"
Williams diminutive frame belied her powerful, soulful pipes. Her initial success in the music industry came as a background singer for artists ranging from Chaka Khan, Anita Baker and Sting. But she would eventually establish her career with release of her first album, "Vesta," in 1986.
Over the years, she had hits including "Once Bitten Twice Shy," "Sweet, Sweet Love" and her signature torch song "Congratulations."
Williams continued to make albums, and was a regular performer on the concert circuit.
She was supposed to perform at the 21st annual "DIVAS Simply Singing!" in Los Angeles next month, put on Ralph. The Oct. 22 show will now pay tribute to her and another late soul singer, Teena Marie.
"She was really excited about doing divas," her friend and fellow entertainer Sheryl Lee Ralph told The Associated Press, adding Williams was also scheduled to be the subject of a TVOne "Unsung" episode.
The 5-foot-3 entertainer gained weight in the 1990s, ballooning to a size 26. She went on a dramatic weight loss program, losing 100 pounds and getting down to a size 6.
She told Ebony magazine that she began gaining weight rapidly after her singing career started to falter. She blamed her size for loss of her recording contract.
"When I lost my record deal and my phone wasn't ringing, I realized that I had to reassess who Vesta was and figure out what was going wrong," she said. "I knew it wasn't my singing ability. So it had to be that I was expendable because I didn't have the right look."
She went on to become an advocate for the prevention of childhood obesity and juvenile diabetes.
Last year, she released a song on iTunes. In an interview last December with Egypt Thompson on the Web show "The Couch," she said she was blessed.
"She had just become such a brand new person," Ralph said. "This is very hard, this is very hard."
Ralph said Williams is survived by an adult daughter.