The 80-year-old actor, best-known for playing Mr. Spock in the original TV series that began in September 1966, formed four fingers into a V for Vulcan sign and intoned to fans Spock's most famous phrase: "Live long and prosper."
Nimoy has said the convention in suburban Chicago celebrating the 45th anniversary of "Star Trek" would be his last.
He spoke for an hour about his life and career, and thanked fans for their support over the years. Some held signs saying: "We love you Leonard! Live long & prosper."
Creation Entertainment organizes the "Star Trek" conventions. Company CEO Adam Malin says the company has toured and collaborated with Nimoy for nearly three decades and that Nimoy "will be missed."