In terms of land area, Piscataquis is one of the largest U.S. counties east of the Mississippi River.

Baxter State Park, a large wilderness preserve, is located in Piscataquis County.

In June 1799, near Piscataquis County's three major rivers, people started clearing land and settling there.

The highest natural point in the county and the state of Maine is Mount Katahdin at 5,271 feet (1,607 meters), while the geographic center is Greeley Landing in the Town of Dover-Foxcroft.

23.6% were of English, 16.4% French, 15.3% United States or American and 11.5% Irish ancestry according to Census 2000.

As of the 2010 United States census, there were 17,535 people, 7,825 households, and 4,948 families residing in the county.

[15] In terms of ancestry, 21.4% were English, 16.5% were Irish, 13.6% were American, 8.7% were German, 5.5% were Scottish, and 5.3% were French Canadian.

[18] Piscataquis County has one of the lowest rates of religious adherence in the United States.

District 3 includes the towns of Bowerbank, Brownville, Lake View Plt, Medford, Milo, Sebec and the Unorganized Territories of Atkinson, Barnard, Ebeeme, Katahdin Iron Works, Orneville, Williamsburg and Northeast Piscataquis County.

[22] In the 2012 Piscataquis County Commissioner District 2 election, Republican candidate James Annis received 52% of the vote.

[24] In the Maine gubernatorial election, 2010, Republican candidate Paul LePage received the most votes in Piscataquis County with 48.4%.

Democratic candidate, Libby Mitchell received the third most votes in the county with 10.9% of the total.

In the Maine gubernatorial election, 2006, Republican candidate Chandler Woodcock received the most votes in Piscataquis County with 37.7%.

Democratic candidate, incumbent governor John Baldacci received 34.5%.

In the Maine gubernatorial election, 2002, Democratic candidate John Baldacci received the most votes in Piscataquis County with 50.4%.

In the Maine gubernatorial election, 1998, Independent candidate Angus King received the most votes in Piscataquis County with 50.2%.

In the United States House of Representatives elections in Maine, 2012, incumbent Democratic candidate Michael Michaud received the most Piscataquis County votes with 53% of the total.

Piscataquis County is one of the most reliably Republican counties in New England, only voting for a someone other than the Republican candidate five times since 1880 — voting for Bull Moose Party nominee Theodore Roosevelt (a former Republican) in 1912, Democrats Lyndon B. Johnson and Hubert Humphrey in 1964 and 1968 respectively, independent Ross Perot in 1992, and Democrat Bill Clinton in 1996.

In 2008, Piscataquis was the only county in New England to vote for John McCain, who won the county by a margin of 355 votes or 3.8%[25] over Barack Obama, with Obama winning Maine by a 17.3% margin over McCain.

There were a total of 30 "write in" votes; 29 of these were for Ron Paul and 1 for Rocky Anderson.

[28][29] Republican candidate Donald Trump carried the county in 2016 while greatly improving on Romney's performance.