Manzi received his B.A. in Classics from Colgate University in 1973, and later received his M.A. in International Relations from the Fletcher School of Law and Diplomacy at Tufts University in Medford, Massachusetts. In 1975, Manzi was a research assistant to William F. Buckley, and journeyed to the Soviet Union with the editorial staff of National Review.Later, Manzi worked as a management consultant at McKinsey & Company.
In 1982, Manzi joined Lotus Development. In 1984, he became President and two years later Chairman and CEO succeeding founder Mitchell Kapor. When Kapor left the company, Manzi steered the company away from desktop application software. He is credited with successfully migrating the company to and creating a new category of network applications. The product, Lotus Notes, was developed by Ray Ozzie and a team of great engineers at Iris Associates, in conjunction with a core team at Lotus. Ultimately the company was sold for a $3.5 billion to IBM. largely on the strength of the potential of Lotus Notes. On October 11, 1995 Manzi announced his resignation from the Lotus division of IBM.
Career after Lotus
On May 25, 2000, Manzi made an investment in Interwise and joined its board. Interwise was sold to AT&T. He is also chairman of Skyword, Inc. and is on the board at Freshdirect. Clover Food Labs, Cargometrics, Elysium Health. He has been chairman of ThermoFisher Scientific (formerly ThermoElectron), a public company in life sciences technology and services with $17 billion in sales and a market cap of more than $50 billion. 
- Buckley, Priscilla. "Living It Up With National Review"
- Feb 1992 What Is It About Jim Manzi? by Rich Karlgaard, UPSIDE at the Wayback Machine
- How to Land a Media Job: Tips for Seniors - March 11, 2009, Glenda Manzi (Southern Methodist University ’70) Three-time Emmy-Award-Winning Producer of News and Documentary Programs for PBS Formerly, Principal and Executive Producer, Botticelli Interactive Lecturer on Media in the 21st Century for Tufts CMS Program, Communications & Media Studies, Tufts University
- Interwise: True Enterprise Conferencing:Interwise Investors Archived March 12, 2006, at the Wayback Machine.
- Jim Manzi - IT Channel - IT Channel News by CRN and VARBusiness:By Barbara Darrow (From the December 12, 2003 issue of CRN)
- "TMO Jim P. Manzi Insider Trades for Thermo Fisher Scientific Inc.". MarketWatch. Retrieved 2 March 2015.
- Darrow, Barbara. 2003 Industry Hall of Fame: Jim Manzi. CRN, December 15, 2003
- Judge, Paul C. and Baker, Stephen. Were Jim Manzi's Big Ideas Too Big?. BusinessWeek, May 26, 1997
- Former Lotus Chief Manzi Heads Up Another Venture. TechWeb.com, December 09, 2003
- Jim Manzi's Article (The End of the Literary Industrial Complex)
- 2003 Industry Hall of Fame: Jim Manzi
- Were Jim Manzi's Big Ideas Too Big?
- Manzi Resigns At Lotus
- InterWise Appoints Former Lotus Chief, Jim Manzi, to Board of Directors
- One-stop site for blogs offered - The Boston Globe
- Willamette University - Jim Manzi
- Chief of I.B.M.'s Lotus Resigns 99 days After Takeover Deal (From the October 12, 1995 New York Times)