The 1900s saw great changes in Ashtabula. Its access to Lake Erie and nearly 30 miles of shoreline helped position Ashtabula as a major shipping and commercial center.During the 1950s, the area experienced growth with its expanding chemical industry and increasing harbor activity, making Ashtabula one of the most important port cities of the Great Lakes. Interesting historical industries in the area included a Rockwell International plant on Route 20 on the western side of Ashtabula that manufactured brakes for the Space Shuttle program as well as the extrusion of depleted and enriched uranium at the Reactive Metals Extrusion plant on East 21st Street, prompting FEMA to, as recently as 1990 (the year the plant ceased operations), place Ashtabula on its list of expected primary nuclear targets for the Soviet Union.

Ashtabula Harbor hosts an annual Blessing of the Fleet community festival. The origin of the Blessing of the Fleet can be traced to Portuguese and Irish fisherman and tugmen who settled in Ashtabula. Sometime in the 1930s, the Blessing of the Fleet was a small, almost private affair in early April conducted by a few tugmen, their parish priest, and an acolyte. By 1950, it had become a public ceremony under the auspices of Mother of Sorrows parish. In 1974, the Blessing of the Fleet became a community affair involving all of Ashtabula's religious and harbor community. Today the Blessing is held annually, usually in late May. The Coast Guard Station and the Harbor Museum and other sites have been established to preserve Ashtabula's maritime heritage.