Pausch died at his home in Virginia, university spokeswoman Anne Watzman said. Pausch and his family moved there last fall to be closer to his wife's relatives.
Pausch was diagnosed with incurable pancreatic cancer in September 2006. His popular last lecture at Carnegie Mellon in September 2007 garnered international attention and was viewed by millions on the Internet.
In it, Pausch celebrated living the life he had always dreamed of instead of concentrating on impending death.
"The lecture was for my kids, but if others are finding value in it, that is wonderful," Pausch wrote on his Web site. "But rest assured; I'm hardly unique."
The book "The Last Lecture," written with Jeffrey Zaslow, leaped to the top of the nonfiction best-seller lists after its publication in April and remains there this week. Pausch said he dictated the book to Zaslow, a Wall Street Journal writer, by cell phone. The book deal was reported to be worth more than $6 million.
At Carnegie Mellon, he was a professor of computer science, human-computer interaction and design, and was recognized as a pioneer of virtual reality research. On campus, he became known for his flamboyance and showmanship as a teacher and mentor.
The speech last fall was part of a series Carnegie Mellon called "The Last Lecture," where professors were asked to think about what matters to them most and give a hypothetical final talk. The name of the lecture series was changed to "Journeys" before Pausch spoke, something he joked about in his lecture.
"I thought, damn, I finally nailed the venue and they renamed it," he said.
He told the packed auditorium he fulfilled almost all his childhood dreams
- being in zero gravity, writing an article in the World Book Encyclopedia and working with the Walt Disney Co.
The one that eluded him? Playing in the National Football League.
"If I don't seem as depressed or morose as I should be, sorry to disappoint you," Pausch said.
He then joked about his quirky hobby of winning stuffed animals at amusement parks
- another of his childhood dreams - and how his mother introduced him to people to keep him humble: "This is my son, he's a doctor, but not the kind that helps people."
Pausch said he was embarrassed and flattered by the popularity of his message. Millions viewed the complete or abridged version of the lecture, titled "Really Achieving Your Childhood Dreams," online.
Pausch lobbied Congress for more federal funding for pancreatic cancer research and appeared on "Oprah" and other TV shows. In what he called "a truly magical experience," he was even invited to appear as an extra in the new "Star Trek" movie.
He had one line of dialogue, got to keep his costume and donated his $217.06 paycheck to charity.
