Established by Oregon State University in 1965 on Yaquina Bay in Newport, the Hatfield Marine Science Center (HMSC) was constructed on land donated by the Port of Newport and funded by grants from the Federal Economic Development Administration. The campaign to build HMSC was driven by three major forces at work in Newport during the 1960s. First, many saw the development of a marine research facility with a public education component as a draw for tourists in a stagnant coastal economy. Another motivating factor was the Department of Oceanography's need for dock and ship support facilities for the research vessel. At the same time, the Yaquina Bay Oyster Laboratory, a research facility established earlier by the university, was looking to expand their operations.

The university's presence on Yaquina Bay dates from 1938, when Fisheries and Wildlife Department Professor Roland Dimick established the Yaquina Bay Oyster Laboratory. Starting out as a floathouse at Sally's Bend, the laboratory expanded into a small land facility where research on various forms of bay life, water quality, and bivalve aquaculture was conducted. From 1946 until 1952, OSC also managed a marine research station in conjunction with the University of Oregon and Portland State College in Charleston, Oregon.

Envisioned as a center for both research and instruction, HMSC began to offer classes in 1966 in the form of a summer courses in zoology and oceanography. Later on, coursework in the Fisheries and Wildlife Department and Biology Program were added to the list of offerings at HMSC. Dormitory housing for undergraduate students on the HMSC campus became available in 1972 with the opening of the Li House. In 1976, instruction at HMSC got a boost with the completion of a library facility and the establishment of a full-time librarian position funded by the university library. Although not part of the center's original mission, public education grew to become one of the most important components at HMSC. In 1966, OSU assigned the task of developing and managing educational programs at HMSC to Extension agent William Wick. Known later as the "Seatauqua" program, HMSC put together a number of tours, workshops, tank talks, and whalewatching opportunities designed to impart marine knowledge to the public.

As a research facility, HMSC hosts scientists from a number of federal and state agencies in addition to those from OSU. A federal presence at HMSC was established early on with the installation of the Environmental Protection Agency in 1966. Other federal research bodies represented at HMSC include: the Fish and Wildlife Service, the National Marine Fisheries Service, the National Oceanic and Atmospheric Administration, and the National Coastal Resources Research and Development Institute. At the state level, the Oregon Department of Fish and Wildlife has conducted research at HMSC since it's founding as well as Oregon Sea Grant. In 1989, HMSC became an OSU Experiment Station branch with the establishment of the Coastal Oregon Marine Experiment Station.

In 1983, the Marine Science Center was officially re-named for Oregon Governor and Senator Mark Hatfield.

Directors of the Hatfield Marine Science Center have included John Byrne (1972-1977), Lavern Weber (1977-2002), and George Boehlert (2002-).