Zuckerman was one of the first staff members of Tripod.com, one of the first successful "dot com" enterprises, where he worked from 1994 to 1999. There, he was in charge of the design and the implementation of the website which, at that time, marketed content and services to recent college graduates. The business model of this website was exclusively based on advertising. After one of the website's major advertisers complained that one of their banner advertisements had appeared on a page that celebrated anal sex, Zuckerman imagined a way to associate an ad with a user’s page without putting it directly on the page. His solution was to open a new dedicated window with only the ad in it. The popup ad was born. While he claims having only written the code to open a new window, since then, he is considered as the inventor of the pop-up ad. In 2000, he founded Geekcorps and 2004, Global Voices Online. He won the MIT Technology Review "Technology in the Service of Humanity" award in 2002 for his work on Geekcorps. Zuckerman has been a senior researcher at the Berkman Center for Internet and Society, where he is also a long-time fellow. His work at the Berkman Center has included research into , as well as the co-founding of Global Voices in collaboration with Rebecca MacKinnon. For some years he was also a contributing writer for Worldchanging.com, where he served as president of the board of directors. In January 2007, he joined the inaugural Wikimedia Foundation Advisory Board. In 2008, he coined the cute cat theory of digital activism. In 2011, he was named by Foreign Policy magazine to its list of top global thinkers, in which he stated the Best idea is "The world isn't flat and globalization is only beginning, which means we have time to change what we're doing and get it right". Also in September of that year, he became the director of the MIT Center for Civic Media. Zuckerman was an Open Society Global Board member, and also sits on the board of directors of Ushahidi, Global Voices, and the Ghanaian journalism training nonprofit, PenPlusBytes. He was interviewed in the 2015 web documentary about internet privacy, Do Not Track. On July 1, 2016, Zuckerman was appointed Associate Professor of the Practice in Media Arts and Sciences at MIT. In 2019, revelations of Media Lab director Joi Ito's connections with Jeffrey Epstein, a convicted sex offender, shed light on the extent of monetary gifts from Epstein to the Media Lab and Ito's startups outside of MIT. Zuckerman resigned from his position as director of the MIT Center for Civic Media, in protest of the Media Lab's involvement with Epstein. He joined the faculty of the University of Massachusetts at Amherst in April 2020.
