Amelio grew up in Miami, Florida, of Italian born parents, and graduated from Miami High School. He received a bachelor's degree, master's degree, and PhD in physics from the Georgia Institute of Technology. While at Georgia Tech, Amelio was a member of the Pi Kappa Alpha fraternity. Amelio joined Bell Labs as a researcher in 1968. In 1970, Amelio was on the team that demonstrated the first working charge-coupled device. He moved to Fairchild Semiconductor in 1971, where he led the development of the first commercial CCD image sensors in the early 1970s, and in 1977 became head of the MOS division. He worked his way up to president of the semiconductor division of Rockwell International, and then its communications systems division. Amelio joined National Semiconductor as president and chief executive in February 1991.
In 1994 Amelio joined the board of directors of Apple. After his resignation from National Semiconductor, Amelio became Apple CEO on February 2, 1996, succeeding Michael Spindler. His salary was a reported $990,000 plus bonuses and a $5 million loan. He also received approximately $100,000 for the use of his business jet by Apple the previous year according to the section "Certain Transactions" in the Apple Proxy Statement for 1996. Amelio cited several problems at Apple including a shortage of cash and liquidity, low-quality products, lack of a viable operating system strategy, undisciplined corporate culture, and fragmentation in trying to do too much and in too many directions. To address these problems Amelio cut costs, reduced Apple's work force by one third, discontinued the Copland operating system project, and oversaw the development of Mac OS 8. To replace Copland and fulfill the need for a next generation operating system Amelio started negotiations to buy BeOS from Be Inc. but negotiations stalled when Be CEO Jean-Louis Gassée demanded $275 million; Apple was unwilling to offer more than $200 million. In November 1996 Amelio started discussions with Steve Jobs's NeXT, and bought the company on February 4, 1997, for $429 million. During Amelio's tenure Apple's stock continued to slump and hit a 12-year low in Q2 1997 that was at least partially caused by a single sale of 1.5 million shares of Apple stock on June 26 by an anonymous party who was later confirmed to be Steve Jobs. Apple lost another $708 million. On the July 4, 1997 weekend, Jobs convinced the directors to oust Amelio in a boardroom coup; Amelio submitted his resignation less than a week later; and Jobs then became interim CEO on September 16. In a 2007 interview with technology journalistGina Smith, Jobs quoted Amelio as having a saying:
Apple is like a ship with a hole in the bottom, leaking water, and my job is to get the ship pointed in the right direction.
It was reported that Amelio's contract gave him about $3.5 million in severance pay, after a $2.3 million performance bonus in 1996.
Amelio is an IEEE Fellow. He received the IEEE Masaru Ibuka Consumer Electronics Award in 1991 for contributions to the development of the charge-coupled device image sensors in consumer video cameras. He has been awarded 16 patents.