January–March

January 25 – Thomas Edison and Alexander Graham Bell form the Oriental Telephone Company.

February 2 – The 5.6 Mla Parkfield earthquake affects central California with a maximum Mercalli intensity of VII (Very strong). Some damage occurred near Imusdale northwest of Parkfield, including cracks in the roads, fallen chimneys, and partially collapsed buildings.[1]

February 5 – Phoenix, Arizona, is incorporated.

February 14 – Pine City, Minnesota, is incorporated.

February 19 – Kansas becomes the first U.S. state to prohibit all alcoholic beverages.

February 22 – Cleopatra's Needle is erected in Central Park, New York City.

March – Barnum & Bailey's "Greatest Show on Earth" opens in Madison Square Garden.

March 4 – James A. Garfield is sworn in as the 20th president of the United States, and Chester A. Arthur is sworn in as the 20th vice president.

March 15 – First plots of Abilene, Texas, are auctioned; the town is incorporated later in the year.

April–June

April 11 – Spelman College is established.

April 14 – The Four Dead in Five Seconds Gunfight erupts in El Paso, Texas.

April 16 – Bat Masterson fights his last gun battle in Dodge City, Kansas.

April 21 – The University of Connecticut is founded as the Storrs Agricultural School.

April 28 – Billy the Kid escapes from his two jailers at the Lincoln County Jail in Lincoln, New Mexico, killing James Bell and Robert Ollinger before stealing a horse and riding out of town.

May 21

The American Red Cross is established by Clara Barton.

The United States Tennis Association (USNLTA) is established by a small group of tennis club members; the first U.S. Tennis Championships are played this year.

June 12 – The USS Jeannette is crushed in an Arctic Ocean ice pack.

July–September

July 2 – Assassination of James A. Garfield: James A. Garfield, President of the United States, is shot by lawyer Charles J. Guiteau at the Baltimore and Potomac Railroad Station in Washington, D.C. He survives the shooting but suffers from infection of his wound, dying on September 19.

July 4 – The Tuskegee Institute opens in Alabama.

July 14 – Billy the Kid is shot and killed by Pat Garrett outside Fort Sumner.

July 20 – Indian Wars: Sioux chief Sitting Bull leads the last of his fugitive people in surrender to United States troops at Fort Buford in Montana.

Summer – First ever summer camp held, on Chocorua Island in Grafton County, New Hampshire.

August 27 – The fifth hurricane of the 1881 Atlantic hurricane season hits Florida and the Carolinas, killing about 700.

September 5 – The Thumb Fire in the U.S. state of Michigan destroys over a million acres (4,000 km²) and kills 282 people.

September 12 – Francis Howell High School (Howell Institute) in St. Charles, Missouri, and Stephen F. Austin High School in Austin, Texas, open on the same day, putting them in a tie for the title of the oldest public high school west of the Mississippi River.

September 19 – President James A. Garfield dies weeks after being shot. Vice President Chester A. Arthur becomes the 21st president of the United States.

October–December

October 5–December 31 – International Cotton Exposition in Atlanta, Georgia.

October 18–21– Yorktown Centennial is observed in Virginia; Yorktown Victory Monument cornerstone is laid.

October 22 – Boston Symphony Orchestra gives its inaugural concert.

October 26 – The gunfight at the O.K. Corral occurs in Tombstone, Cochise County, Arizona.

October 29 – Judge magazine is first published.

November 17 – The trial of Charles J. Guiteau begins in Washington, D.C.

December 4 – The first edition of the Los Angeles Times is published.

December 28 – Virgil Earp is ambushed in Tombstone and loses the use of his left arm.