
Weeks Bay Reserve is the only preserve in Alabama within the National Estuarine Research Reserve System (NERRS), a nationwide network of 27 coastal reserves managed for long-term research and education and interpretative programs on estuarine habitats. The goal of NERRS is to establish and manage, through cooperative arrangements between federal and state agencies, a nationwide system of reserves representing the different coastal regions and estuarine ecosystems that exist in the United States.

The establishment of the reserve dates to the late 1970's, when the Nature Conservancy (TNC), a national conservation group, purchased 615 acres of coastal land with the intent of donating it to the federal government to be included in Bon Secour National Wildlife Refuge. After the federal government decided not to include the land as part of the refuge, in 1980 TNC agreed to donate the land to the state of Alabama if it was designated as an estuarine reserve. Over the next five years, the Alabama Department of Conservation and Natural Resources and the National Oceanic and Atmospheric Administration worked to establish the reserve, culminating in the final approval of the management plan for the sanctuary in November 1985. During this five-year development period, in 1981 and 1982, the preserve's boundaries were expanded when the Alabama state government purchased additional acreage and TNC donated more land. In 1986, Weeks Bay was officially designated as the nation's 16th National Estuarine Sanctuary, with a total of 3,028 acres. With the inclusion of contiguous submerged lands and waters and some small additional land acquisitions, the current acreage has more than doubled.
In 1990, private citizens and representatives from state and local agencies and educational institutions established the non-profit Weeks Bay Foundation to serve as the fund-raising arm of the preserve. The foundation seeks funding through donations, grants, and membership fees, assists in property acquisitions, and conducts special programs. The foundation staff is governed by an elected Board of Directors. The foundation currently has more than 550 members who assist the staff in education, research, and environmental protection functions, including such projects as water quality monitoring and educational outreach programs. The preserve features the 4,000-square-foot Weeks Bay Reserve Interpretive Center, constructed in 1994 to house informational displays and live animal exhibits and offer educational programs for school groups and other organizations. From the center, visitors can traverse 5,000 feet of boardwalk and more than two miles of nature trails that take them through a native pitcher plant bog, a butterfly and hummingbird garden, archaeological displays, and estuarine habitats. A research facility with a 50-seat auditorium completes the facilities infrastructure. The reserve also participates in a Web-based distance-learning project in cooperation with Faulkner State Community College and professional development programs for teachers.

The threats to Weeks Bay Reserve are those common to all of the Gulf Coast and include water pollution, habitat loss caused by soil sedimentation from construction, and development on buffer wetlands that destroys habitat. The reserve plans to purchase lands that become available for sale to mitigate these issues. The most significant and unexpected threat to the bay to date occurred in April 2010, when millions of gallons of oil gushed into the Gulf of Mexico after an underwater explosion on an oil rig owned by Deepwater Horizon, under contract with British Petroleum (BP). The long-term effects of the Gulf oil disaster are still unknown, but during the spill itself, the nearby town of Magnolia Springs took the initiative and purchased an oil-absorbent boom after the absence of a timely response by BP or the federal government. The boom was deployed across the mouth of the bay with the assistance of local fire departments. The barrier and the fact that very little of the oil spread into the immediate Weeks Bay area as a result of its geographic location apparently spared it from major damage. Sampling and analysis of water and soils in the area is ongoing.
In August 2014, the Alabama Department of Conservation and Natural Resources completed a reef restoration project that was carried out by contractor Alabama Marine Resources Division. The effort involved the introduction of more than a thousand cubic yards of oyster shells on the site of a defunct reef at the mouth of Weeks Bay that will serve as habitat for many types of marine creatures. As it develops, the reef will also protect the habitats within Weeks Bay and the surrounding landscape from the effects of storm surges.