[citation needed] Prior to the European colonization, the Millvale area was the starting point of the Venango Path, a Native American trail which led Lake Erie.

During a major raid by Chief Tewea of the Lenape and Captain François Coulon de Villiers of the French, Girty's stepfather was taken captive, tortured, and killed.

Due to his difficulty living with Europeans, Simon settled on the Venango Path near a creek which now bears his name.

Allegheny City later purchased 164 acres of the Sample estate to place a poor farm on the site, which ran for twenty-three years.

The poor farm brought industry into Millvale, including an 1847 forge that became the rolling mill owned by Henry Phipps.

[8][9] In 1849, Herrs Island and the adjacent riverfront land of Reserve Township spanning from its northeastern boundary near Girty's Run downriver to Butcher's Run were incorporated as the Borough of Duquesne, distinct from the modern city of the same name.

A massive influx of immigrants searching for work at the nearby railroad occurred at what is now the 40th Street Bridge resulting in the construction of a passenger rail station.

[10] In 1868, Duquesne was partitioned with the downriver portion annexed by Allegheny City, and the land upriver of the northern end of Herrs Island joined with adjacent lands to the north and east taken from Shaler Township to form Millvale.

[3][5] The borough expanded after the American Civil War and was connected to Lawrenceville via the Ewalt Covered Bridge and a narrow gauge railroad that would become part of Pittsburgh’s trolley system.

[9] At the start of the Great Depression, Millvale was a target of the Works Progress Administration which attempted to reign in Girty’s Run Creek.

The borough was also an important industrial center for America's effort in World War II.

[11] America’s energy crisis and the downfall of the steel industries later led to a steady decline in population which continues through the present day.

Millvale regularly collaborates with its northern riverside neighbors of Etna and Sharpsburg.

The total unemployment rate was 4.3%[4] Millvale was also home to 134 veterans, 114 of which were male and 20 of which were female.

[4] St. Nicholas Roman Catholic Church, built in 1901, was the first Croatian parish in the United States.

[46] Millvale Riverfront Park provides a 1.7 mile bike and walking trail that provides access from Millvale to Pittsburgh's North Shore, PNC Park, and Acrisure Stadium along the Three Rivers Heritage Trail.

Other park amenities include a beautiful pavilion with riverfront access and a full kitchen, Mr. Smalls Skate Park, bike and boat rental, Millvale Marina, kayak and rowing boat launch access, fishing, a tackle and bait shop, and more.

The Riverfront Park is also home to the annual BrewFest in August and the newly launched Harvest Moon Wine Festival in the Fall.

[47] Most recently, the Millvale Community Library has been launched as an all-volunteer effort of community members to take several vacant buildings and lots and turn them into a multi-use space centered on creating Millvale's first public library and associated garden space.