Dessler worked in the energy group at The First Boston Corporation doing mergers and acquisitions analysis in the mid-1980s. He left his job as an investment banker on Wall Street in 1988 to go to graduate school in chemistry. After receiving his Ph.D. in 1994, Dessler did two years of Postdoctoral research at NASA's Goddard Space Flight Center and then spent nine years on the research faculty of the University of Maryland from 1996 to 2005. Dessler went on to become an Associate Professor of Atmospheric Sciences at Texas A&M University from 2005 to 2007 and has been a tenured Professor of Atmospheric Sciences there since 2007.
He served as an editor for the American Geophysical Union Books Board from 1997 to 2002, and an associate editor for the Journal of Geophysical Research in 2002.
Dessler also served as a Senior Policy Analyst in the White House Office of Science and Technology Policy for the last year of the Clinton administration. That experience was the basis for the book he co-authored, The Science and Politics of Global Climate Change: A Guide to the Debate.
He also published a blog for Grist magazine from 2006 to 2009.  He later stated, "At first, I was enamoured with blogging, until I realized how repetitive it was to keep answering the same questions. I decided I wanted a more high-impact way to spend my time." The New York Times said the results of his 2004 article in the Journal of Climate written with Ken Minschwaner placed them, "in the middle between the skeptics and those who argue that warming caused by burning of fossil fuels could be extremely severe." The authors wrote a joint letter to the editor in response objecting to the impression given by the article that their "research goes against the consensus scientific view that global warming is a serious concern." They went on to state their work did not argue against the seriousness of the problem and that the potential effects were so serious "that slight overestimates of this warming make little difference -- just as reducing the size of a firing squad from 10 shooters to nine makes little difference to the person being executed." A 2009 article in Science showed "warming from rising carbon dioxide should also lead to increased water vapor and additional warming, doubling the warming effect of the carbon dioxide." according to Kenneth Chang of The New York Times.
Currently, Dessler is an editor of the Bulletin of the American Meteorological Society and president-elect of the Global Environmental Change section of the American Geophysical Union. He is also the Director of the Texas Center for Climate Studies and holder of the Rita A. Haynes Chair in Geosciences at Texas A&M University.