While continuing his education at the University of California, Davis, DeLong had originally planned on becoming a medical technologist, but after a meeting and working as an undergraduate researcher with bacteriologist Paul Baumann, he found a new interest in marine microbiology.

[2] He graduated with a Bachelor of Science degree in bacteriology at UCD in 1982 and moved to the Scripps Institution of Oceanography, where he received a Ph.D. in marine biology after finishing doctoral work with Art Yayanos in 1986.

In the years following, DeLong's work took him to the Monterey Bay Aquarium Research Institute and it is during his time there that he made a crucial discovery in the understanding of the Earth's carbon and energy cycles.

At MIT, his collaborations with CMORE and Monterey Bay Aquarium Research Institute colleagues, he discovered of highly synchronized microbial populations having oscillating patterns of gene expression[6] across many species.

In 2014, DeLong relocated to the University of Hawaii, where he serves as co-director for the Center for Microbial Oceanography: Research and Education, C-MORE[7] and the Simons Collaboration on Ocean Processes and Ecology, SCOPE.