She was 99 and was set to turn 100 on Jan. 17.
White's death was confirmed by her agent and close friend, Jeff Witjas, to NBC News during a phone call.
"Even though Betty was about to be 100, I thought she would live forever," Witjas said. "I will miss her terribly and so will the animal world that she loved so much. I don't think Betty ever feared passing because she always wanted to be with her most beloved husband Allen Ludden. She believed she would be with him again."
Certified by Guinness World Records as having the longest-running career of any female television entertainer, White got her start in showbiz sometime in 1939 on a television show, dancing in her high school graduation clothes. But over the ensuing decades, White endeared herself to generations with a series of memorable roles, including on "The Mary Tyler Moore Show" (1973-1977), "The Golden Girls" (1985-1992) and "Hot in Cleveland" (2010-2015).
As GIFs of Golden Girls one-liners spread across the internet via social media and White’s fame seemed to rise even further in the waning years of her ninth decade. She spoke to People magazine ahead of her centenary and shared her secret to longevity: “I try to avoid anything green,” she joked. “I guess it’s working.”
White appeared to embrace her viral fame as the internet claimed her as one of its favorite famous people. Know Your Meme, the meme database, includes several entries featuring White, including wholesome memes featuring the actress not being able to play with legos beyond her 99th birthday.
In a Snickers commercial that premiered during the 2010 Super Bowl telecast, she impersonated an energy-sapped dude getting tackled during a backlot football game.
“Mike, you’re playing like Betty White out there,” jeered one of his chums. White, flat on the ground and covered in mud, fired back, “That’s not what your girlfriend said!”
After a successful Facebook campaign that year, White became the oldest person to host "Saturday Night Live" at the age of 88.
A month later, cable’s TV Land premiered “Hot In Cleveland,” the network’s first original scripted series, which starred Valerie Bertinelli, Jane Leeves and Wendie Malick as three past-their-prime show-biz veterans who move to Cleveland to escape the youth obsession of Hollywood.
They move into a home being looked after by an elderly Polish widow — a character, played by White, who was meant to appear only in the pilot episode. But White stole the show, and the salty Elka Ostrovsky became a key part of the series, an immediate hit.
Born Betty Marion White on Jan. 17, 1922, in Oak Park, Illinois, the future TV star was the only child of an electrical engineer father and homemaker mother. The family moved much closer to the center of the entertainment industry, Los Angeles, two years later.
White started in television as an assistant, but she worked her way up to become one of the first female producers in the business in 1952 with her sitcom "Life With Elizabeth," developed with George Tibbles.
“George would drive me to the studio and we'd talk about what we were going to do, ad lib some things,” White told The Hollywood Reporter in 2010. “He'd write the script and we'd film it. When he drove me home, we'd talk about next week's show.”
The year before the show premiered, she earned the first of her 21 Primetime Emmy Award nominations (she would win five) on her way to becoming a staple on television as both a go-to guest star and a regular on the game show circuit.
White also co-hosted NBC's Macy's Thanksgiving Day Parade from 1963 to 1972 before joining "The Mary Tyler Moore Show" in 1973 and earning more widespread acclaim.
But White arguably became best known much later in life for her quick one-liners as the gullible yet lovable Rose Nylund on "The Golden Girls," which aired on NBC from 1985 to 1992. White starred alongside Bea Arthur, Rue McClanahan and Estelle Getty, all of whom were younger than her but all of whom she outlived.
The role proved so popular that White reprised it for three other shows — "The Golden Palace," "Empty Nest" and "Nurses" — and played a succession of similar characters on other shows.
White married three times, saying her only regret about her third husband, game show host Allen Ludden, whom she married in 1963, was that she didn't marry him sooner, NBC's "TODAY" show reported in 2015.
She never remarried after he died of stomach cancer in 1981.
White was an avid animal activist and worked with the Morris Animal Foundation and the Los Angeles Zoo for more than 40 years.
"I have to keep acting so that I can afford to keep doing my charity work," she told The Hollywood Reporter. "I'm actually the luckiest old broad alive. Half my life is working in a profession I love and the other half is working with animals. I couldn't ask for more."
Her passion for the cause was so great that she famously turned down a role in the 1997 film "As Good as It Gets" because there was a scene in which a dog was mistreated.
Not that she was hurting for work: White remained vivaciously sharp-witted until her death, with a wicked sense of humor that transcended her age. She continued to act in television series — such as “Hot in Cleveland,” “Bones” and “Community” — and the occasional movie, such as 2009's "The Proposal," later in her life.
White won eight Emmys in total (including prime-time and daytime awards) and a Grammy Award for best spoken word album for "If You Ask Me (And of Course You Won't)." She was also honored with a star on the Hollywood Walk of Fame — right next to Ludden's.
Over her long and storied career, White stayed relevant by doing what she does best: never missing the chance to deliver a good punchline.
"Somebody said something the other day about 'first lady of television,'" she said during her speech at the 2018 Emmy Awards. "And I took it as a big compliment."
"And then I heard her talking to her daughter a little later, she said, 'First lady, yes, she's that old. She was the first one, way, way back,'" White said. "But little did I dream then that I would be here."
Stars across the internet reacted to White's passing.
Ryan Reynolds, who the day before White's passing was responding tongue-in-cheek to a joke she made about him in her upcoming People magazine profile, tweeted Friday: "The world looks different now."
"She was great at defying expectation. She managed to grow very old and somehow, not old enough. We’ll miss you, Betty. Now you know the secret."
Also in response to news of White's forthcoming magazine profile, actor and comedian Steve Martin on Thursday recounted meeting White in 1974 when he was an "obscure" opener for Linda Ronstadt.
"I loved Betty White, so I went up to them: 'I’m so honored to meet you both.' And then I said, 'Isn’t Linda great?' She said, 'We came to see you.' I said, 'Why?' 'Because we heard you were funny.' I was elated."
The U.S. Army even weighed in on Twitter, saying "We are saddened by the passing of Betty White."
"Not only was she an amazing actress, she also served during WWII as a member of the American Women's Voluntary Services. A true legend on and off the screen."
"Our Sue Ann Nivens, our beloved Rose Nylund, has joined the heavens to delight the stars with her inimitable style, humor, and charm," wrote actor George Takei.