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Settled in 1812 and platted in 1872, DuBois was incorporated as a borough in 1881 and as a city in 1914. The town was founded by John Rumbarger, for whom the town was originally named. The Rumbarger Cemetery is all that survives of John Rumbarger's "original settlement" in the city of DuBois. The town was later renamed for local lumber magnate John DuBois, who came from a longstanding American family of French Huguenot descent. Many of the town's original buildings and homes were funded and or donated by Mr. DuBois's lumber mill. In 1938, his nephew, John E. DuBois, donated the family mansion and estate as a permanent home for the DuBois Campus of Penn State University. While DuBois was founded as a lumber town, the mining of bituminous coal quickly became the chief industry in DuBois. Over the years there have been numerous unsuccessful attempts in 1989, 1995, and 2002 to combine the city with the surrounding Sandy Township, but in 2021 voters in both municipalities successfully voted to consolidate into a new third class city, anticipated to take effect between 2024 and 2026. Combined, the population of DuBois and Sandy Township is approximately 18,000 people. The Commercial Hotel, since demolished, was listed on the National Register of Historic Places in 1985, and the DuBois Historic District was listed in 1997.

DuBois is located in northwestern Clearfield County at (41.120304, 78.761962). It is surrounded by Sandy Township. It is bordered to the southwest by the community of Sandy and to the southeast by the community of Oklahoma. According to the U. S. Census Bureau, the city has an area of , of which is land and , or 1.24%, is water. Sandy Lick Creek flows through the city from east to west. It is a tributary of Redbank Creek, part of the Allegheny River/Ohio River basin.

DuBois has a humid continental climate (Köppen Dfb). Winters are cold with periods of heavy snowfall, while summers are warm and humid. The monthly daily average temperature in July is , while the same figure for January is ; the annual mean is .

As of 2013, the Medium Household Income was $34,340. Ninety five percent of adults 25 and over have a high school diploma, 22% hold a bachelor's degree or higher and 10% have a Graduate Degree.

As of the census of 2010, there were 7,794 people. The racial makeup of the city was 96.3% White, 0.60% African American, 0.10% Native American, 0.90% Asian, 0.0% Pacific Islander, 1.1% from two or more races, and 1.2% Hispanic or Latino. In the city, the population was spread out, with 22.4% under the age of 18 and 16.4 who were 65 years of age or older. Females were 52.5% of the population.

As of the census based at the airport. The airport serves general aviation, and Southern Airways Express offers scheduled non stop service to Washington Dulles International Airport and Pittsburgh International Airport under the Essential Air Service.

The city is located just south of Interstate 80 with exits at mile markers 97 and 101. DuBois is located on U. S. Route 219, which connects with Buffalo, New York, to the north and Johnstown, Pennsylvania, to the south. The city is located 3 mile (5 km) north of U. S. Route 322, which locally connects the city with Reynoldsville west bound and Clearfield east bound and to Atlantic City, New Jersey to the east and Cleveland, Ohio to the west. U. S. Route 119 begins as Blinker Parkway just south of the city. It connects the city with Punxsutawney and eventually leads to southwestern Pennsylvania and West Virginia. Pennsylvania Route 255 begins in the northern part of the city and follows East DuBois Avenue, then becoming the Bee Line highway, connecting to the city of St. Marys, becoming the Million Dollar Highway.

Fullington Trailways operates a bus terminal via Fullington Auto Bus Company with a station located on Rockton Road just past the intersection of Maple Avenue and Shaffer Road. It is part of the Trailways Transportation System which interlines with other carriers that includes Greyhound. DuBois is a hub for Fullington Trailways; all of its routes to Harrisburg, State College, Scranton–Wilkes Barre, Pittsburgh, and Buffalo run through DuBois.

Local businesses are diverse; producing paper, lumber, food products, concrete, utility meters, machinery, and equipment, which are shipped to customers around the world via the area's extensive transportation infrastructure. The DuBois Mall is a regional retail center serving the Tri County area with national stores including Old Navy and JC Penney.

Penn Highlands Healthcare is an extensive healthcare organization headquartered in DuBois, and DuBois' largest employer. It serves patients from ten counties through affiliates: Penn Highlands Brookville, Penn Highlands Clearfield, nationally recognized Penn Highlands DuBois (formerly the DuBois Regional Medical Center), and Penn Highlands Elk.

DuBois receives television programming from the Johnstown Altoona State College, PA media market.

The DuBois Micropolitan area is served by The Courier Express, a Monday Friday evening daily newspaper with a circulation of approximately 10,000 homes and businesses. It covers the DuBois area of Clearfield County and most of Jefferson County, plus the southern half of Elk County in depth, reaching up into Johnsonburg and southern McKean and Forest counties. It was established in 1944 when the Daily Courier (founded as the Weekly Courier in 1879) and the Daily Express (founded as the Express in 1883) consolidated to become The Courier Express. Tri County Sunday is printed on Sundays with a circulation of approximately 16,000. It covers the area of The Courier Express, plus wide circulation in Cameron, southern McKean, Clarion and Forest counties.

Regional advanced education resources include Pennsylvania State University – DuBois Campus, and Triangle Tech all located in DuBois, with Lock Haven University – Clearfield Campus, South Hills School of Business and Technology – State College and Clarion University a short commute away.

One of DuBois' recreational assets is Treasure Lake, a semi private, gated residential community consisting of over Community recreational amenities consist of two lakes for boating and fishing, three beaches, two PGA rated 18 hole golf courses, clay & hard tennis courts, two swimming pools, horse stables, and a campground that offers cottage rentals and camping sites. Additionally, Treasure Lake has two pro shops, a marina, a country store, two concession stands, a town center, and a salon.

The DuBois Country Club is a century old club with a public golf course with a clubhouse.

Cook Forest is the most important tract of virgin timberland to be found in Pennsylvania and is a 35 mile drive from DuBois. Major Israel McCreight of DuBois was an early advocate, promoter, and steward of the Cook Forest State Park, the first Pennsylvania State Park acquired to preserve a natural landmark. Cook Forest features 27 marked trails totaling 29 miles for hiking. The terrain is of rolling hills and cool valley streams. Scenic areas include the old growth forest, Fire Tower/Seneca Point and the Clarion River. Among Cook Forest's primary attractions is the "Forest Cathedral" area of old growth white pine and hemlock, some trees of which top 180 feet. About 5,000 acres are open to hunting, trapping, and the training of dogs during established seasons. Common game species are deer, wild turkey, bear, and squirrel. The Clarion River flows along the park border and provides fishing for trout, warm water game fish and panfish. Visitors can canoe or kayak down the river.

DuBois is building a strong reputation for local entertainment and the arts in the tri county area. More traditional arts can be found at the Winkler Gallery of Fine Arts, founded by local artist Perry Winkler. The Winkler Gallery of Fine Arts opened its doors in December 2003 as a co op for local artists to display and sell their work to the public. The gallery hosts the annual DuBois Arts Festival. Along with supporting the local artist community, the gallery provides art education for the residents of the DuBois area through artist workshops in several mediums such as stained glass, silk painting, and watercolors. Theater groups "Reitz Theater Players" and "Cultural Resources Inc." perform a selection of theater productions each year at the Paul G. Reitz Theater in downtown DuBois.

There seems to be some debate as to exactly when Frank Hahne came to DuBois and broke ground on his own facility. One source claims 1898, another 1897. It seems most likely that this occurred between April and the end of 1896. It was on April 16, 1896, that the DuBois Weekly Courier reported: "Some new developments in connection with the brewery may be looked for in the near future." There were a number of reasons Hahne chose the DuBois site for his facility, but the most frequently cited was the excellence of the water supply. He purchased surrounding the local reservoir to protect the watershed from pollution. By 1906, the brewery had four products on the market: DuBois Wurzburger, Hahne's Export Pilsener, DuBois Porter, and DuBois Budweiser. The Budweiser name would be at the center of controversy for 60 years between DuBois Brewing and Anheuser Busch. The DuBois brands soon traveled far and wide for a brewery of its size, ranging up to 150 mile (241 km) away and selling well in Buffalo, Erie and Pittsburgh. The brewery's 300 barrel kettle was kept busy churning out brands, while the left over grain materials were pressed and sold for cattle feed and grist mills in the rural areas surrounding DuBois. As with many other American breweries, DuBois Brewing moved right along until 1918 and the advent of Prohibition. The brewery shifted production to "near beer" and soft drinks and opened the H&G Ice Company. According to the April 7, 1933, DuBois Courier, the brewery won the honor of being one of only two breweries in the entire nation that had never violated or been suspected of violating the Prohibition laws since the 18th Amendment went into effect. As a result, DuBois Brewing Company was issued license number G 2, allowing them to resume brewing immediately upon the enaction of the 21st Amendment. Frank Hahne died in 1932, and the brewery was passed to his only son, Frank Hahne Jr., whose own only son died in infancy, leaving the family without an heir. Hahne Jr. sold the brewery to Pittsburgh Brewing in 1967. The brewery was torn down in late 2003.