He "passed away this morning after a long battle with chronic obstructive pulmonary disease at his home in Bel Air," his rep confirmed in a statement.
The actor first announced that he was suffering from the illness last year. "I quit smoking 30 [years] ago," Nimoy Tweeted at the time. "Not soon enough."
"Smokers, please understand," he continued. "If you quit after you're diagnosed with lung damage it's too late."
Nimoy was reportedly hospitalized with chest pains earlier this week.
The actor's Star Trek co-star William Shatner, was heartbroken on hearing the news. "I loved him like a brother," said Shatner in a statement to PEOPLE. "We will all miss his humor, his talent, and his capacity to love."
George Takei, who played Sulu on the series, told Andrea Mitchell Reports on MSNBC: "You know, the word extraordinary is often overused, but I think it's really appropriate for Leonard.
"He was an extraordinarily talented man, but he was also a very decent human being. His talent embraced directing as well as acting and photography. He was a very sensitive man."
Before he played Spock, he appeared on ABC daytime soap opera General Hospital in 1963 as Bernie, a pill pusher who showed up at Peggy Mercer's house with a delivery for Roy Lansing.
Nimoy is survived by his wife, Susan Bay Nimoy, his children and grandchildren. A private memorial service is being planned by the family.