The year 1881 in science and technology involved some significant events, listed below.

• 22 May – John Tebbutt discover the long-period comet, C/1881 K1 (also known as the Great Comet of 1881, Comet Tebbutt, 1881 III, 1881b).^[1]

• October – Charles Darwin publishes his last scientific book The Formation of Vegetable Mould through the Action of Worms.
• L. S. Poliakov describes the wild horse discovered by Nikolai Przhevalsky in Mongolia in 1879 as a new species, Przewalski's Horse (Equus przewalski poliakov).^[2][3]
• The first systematic study in forensic entomology is conducted by physician and entomologist Hermann Reinhard in Germany.^[4]

• Friedrich Beilstein publishes the first edition of his Handbuch der organischen Chemie.

• The birch bark Bakhshali manuscript, incorporating perhaps the earliest known use of mathematical zero, is unearthed near Bakhshali in British India.
• Publication in England of a pioneering study in industrial archaeology, H. A. Fletcher's "The archaeology of the west Cumberland iron trade".^[5]

• Simon Newcomb makes the first statement of Benford's law.^[6]

• July 13 – Dr. George Goodfellow performs the first laparotomy to remove a bullet.
• September 25 – The first modern Caesarean section is performed successfully by German gynecologist Ferdinand Adolf Kehrer in Meckesheim using the transverse incision technique.
• December – Eduard von Hofmann carries out autopsy studies of the nearly 400 victims of the Vienna Ringtheater fire, carbon monoxide poisoning being held an underlying cause of death.
• Louis Pasteur discovers a vaccine for anthrax.
• Carlos Finlay, a Cuban doctor, first proposes that yellow fever is transmitted by mosquitoes rather than direct human contact.^[7]
• French obstetrician Étienne Stéphane Tarnier introduces a form of neonatal incubator (couveuse) for routine care of premature infants at the Paris Maternité.^[8]
• English ophthalmologist Waren Tay publishes the first description of the genetic disorder which will become known as Tay–Sachs disease.^[9]
• approx. date – The non-invasive sphygmomanometer, for the measurement of blood pressure, is invented by Samuel Siegfried Karl von Basch.^[10]

• March 1 – The Cunard Line's SS Servia, the first steel transatlantic liner, is launched at J. & G. Thomson's yard at Clydebank in Scotland.^[11]
• May 16 – The Gross-Lichterfelde Tramway, the world's first electric tramway, is opened in Berlin by Siemens & Halske.^[12]
• June – The positive-buoyancy powered submarine "Fenian Ram" (Holland Boat No. II), designed by John Philip Holland, is first submersion-tested in New York City.
• September 26 – Godalming in England becomes the first town to have its streets illuminated by electric light (hydroelectrically generated).^[13]
• October 10 – Richard D'Oyly Carte's Savoy Theatre opens in London, the world's first public building to be fully lit by electricity, using Joseph Swan's incandescent light bulbs.^[11][14][15] The stage is first lit electrically on December 28.^[16]
• December 21 – SS Aberdeen, the first oceangoing ship successfully powered by a triple expansion steam engine, designed by Alexander Carnegie Kirk, is launched at Robert Napier and Sons' yard at Govan in Scotland.
• Peter Herdic patents the Herdic horse-drawn cab in the United States.

• Copley Medal: Karl Adolph Wurtz^[17]
• Wollaston Medal for Geology: Peter Martin Duncan

• January 29 – Alice Catherine Evans (died 1975), American microbiologist.
• January 31 – Irving Langmuir (died 1957), American chemist.
• March 17 – Walter Rudolf Hess (died 1973), Swiss physiologist, recipient of the Nobel Prize in Physiology or Medicine.
• April 28 – Edith A. Roberts (died 1977), American plant ecologist.
• May 1 – Pierre Teilhard de Chardin (died 1955), French paleontologist and philosopher.
• August 6 – Alexander Fleming (died 1955), British bacteriologist.
• September 18 – Vera Lebedeva (died 1968), Soviet Russian pediatrician.
• October 4 – George Constantinescu (died 1965), Romanian engineer.
• October 11 – Lewis Fry Richardson (died 1953), British mathematical physicist.
• October 22 – Clinton Davisson (died 1958), American physicist.
• November 9 – Margaret Reed Lewis (died 1970), American cell biologist.
• November 13 – Ludwig Koch (died 1974), German Jewish animal sound recordist.

• February 3 – John Gould (born 1804), English zoologist.
• March 26 – Lovisa Åhrberg (born 1801), Swedish surgeon.
• May 14 – Mary Seacole (born 1805), Jamaican-born nurse.
• May 19 – Joseph Barnard Davis (born 1801), English craniologist, physician and anthropologist.
• May 26 – Jakob Bernays (born 1824), German philologist.
• June 16 – George Rolleston (born 1829), English physician and zoologist.
• June 23 – Matthias Jakob Schleiden (born 1804), German biologist.
• June 29 – Maurice Raynaud (born 1834), French physician.
• July 27 – Hewett Watson (born 1804), English biologist.
• October 31 – George W. DeLong (born 1844), American Arctic explorer.
• November 30 – Jean-Alfred Gautier (born 1793), Swiss astronomer^[18]