[4] The settlement at its mouth was likewise called Venango, which since March 3, 1871, has been the South Side of Oil City.

George Bissell, a Yale University chemistry professor, and Edwin L. Drake, a former railroad conductor, made the first successful use of a drilling rig on August 28, 1859, near Titusville.

In 1861, it was the location of Wamsutta Oil Refinery, the first business venture of Henry Huttleston Rogers, who became a leading United States capitalist, businessman, industrialist, financier, and philanthropist.

After joining Standard Oil, Rogers invested heavily in various industries, including copper, steel, mining, and railways.

Rogers amassed a great fortune, estimated at over $100 million, and became one of the wealthiest men in the United States.

He was also a generous philanthropist, providing many public works for his hometown of Fairhaven, Massachusetts, and financially assisting helping such notables as Mark Twain, Helen Keller, and Dr. Booker T. Washington.

Perhaps in one of history's ironies, another resident of Venango County about the same time as Henry and Abbie Rogers was a little girl named Ida M. Tarbell, whose father was an independent producer whose small business was ruined by the South Improvement Company scheme of 1871 and the conglomerate which became Standard Oil.

Introduced to each other in 1902 by their mutual friend Twain, Tarbell, who had become an investigative journalist and Rogers, who knew of her work, shared meetings and information over a two-year period which led to her epoch work, The History of the Standard Oil Company, published in 1904, which many historians feel helped fuel public sentiment against the giant company and helped lead to the court-ordered break-up of it in 1911.

43.9% English or Welsh, 12.5% were of German, 11.1% American, 9.9% Irish, 8.3% Scotch-Irish, 2.8% Dutch, 2.1% Italian, and 1.6% French ancestry.

The United States Office of Management and Budget[15] has designated Venango County as the Oil City, PA Micropolitan Statistical Area (μSA).

In 1984, Venango County actually voted fractionally more Democratic than the nation at-large due to hostility towards Reaganomics in industrial districts, and in the 1992 and 1996 elections it came within two points and one point, respectively of voting for Democrat Bill Clinton, but by 2016 Donald Trump had gained 68.1 percent to Hillary Clinton's 26.8 percent – figures which were long typical of the county.

For instance, a Canadian firm proposed drilling several large mines and allowing oil to flood the tunnels.

The following cities, boroughs and townships are located in Venango County: Census-designated places are geographical areas designated by the U.S. Census Bureau for the purposes of compiling demographic data.