A number of indigenous cultural sites have been identified along the coast adjacent to the park including middens and stone artefact scatters. There have been no archaeological sites identified within the park, however local indigenous communities still hold a strong affiliation with the marine and coastal environment of the area.

Notable sites within the park relating to European settlement include:

• Gibson's steps and tunnel adjacent to the park, dating back to the 1880s - constructed to provide access through a cliff to the beach;
• Marie Gabrielle anchors near Moonlight Head, from a shipwreck in 1869 - an iron anchor and part of the capstan from the French barque. This ship was on route from China with a load of tea when it hit the reef after being forced ashore by strong winds;
• Immediately adjacent to the park is the Point Ronald tunnel and Breakwater - features a river diversion tunnel constructed through rock at the base of the cliff at Point Ronald.

Bass Strait was a major shipping route supplying the growing colonies of Victoria and New South Wales. Five ships, comprising both immigrant ships and traders, are located in or near this park. The Loch Ard was wrecked in 1878. Fifty-two lives were lost. The two survivors were cared for at the Glenample Homestead. Four casualties from the wreck are buried in the Loch Ard cemetery. Other shipwrecks in the Twelve Apostles Marine National Park include the Marie Gabrielle, mentioned above and the Fiji, an Irish barque that ran aground in 1891 after losing its way near Cape Otway in heavy seas. Twelve lives were lost in this wreck. Both of these ships are found on a stretch of coast known as Wreck Beach at Moonlight Head.