The 49-year-old model and designer had been dating the Rolling Stones frontman since 2001 following his split from wife Jerry Hall.
She is understood to have been found this morning at a property in Manhattan.
Miss Scott's assistant found her hanged this morning, a law enforcement official said. No note was found and there was no sign of foul play.
A spokesman for Sir Mick, 70, who is thought to be on tour in Australia, said: "He is completely shocked and devastated by the news."
Miss Scott, who was adopted by Mormon parents and raised in Roy, Utah, had her own fashion label popular with celebrities. She was a fixture on Sir Mick's arm and, at around 6ft 3ins, towered over her famous boyfriend.
She founded her high-end label in 2006 and recently created a more affordable line of clothes with Banana Republic.
On the red carpet, she has dressed stars like Nicole Kidman, Oprah Winfrey, Sarah Jessica Parker and Angelina Jolie.
"This is a horrible and tragic loss," said singer Madonna. "I'm so upset. I loved L'Wren's work and she was always so generous with me."
Just last month Miss Scott cancelled her London Fashion Week show, due to reported production delays.
Make-up artist Bobbi Brown collaborated with Miss Scott last month on a cosmetics line called the Bobbi Brown x L'Wren Scott Collection.
"I am devastated by the tragic news about L'Wren," Ms Brown said on her website. "She was a visionary designer who I very much enjoyed working with, but she was also smart and kind. My thoughts and heartfelt condolences go out to her loved ones during this very sad time."