Harmon Northrop Morse synthesized paracetamol at Johns Hopkins University in 1877, but it was not until 1887 that clinical pharmacologist Joseph von Mering tried paracetamol on humans.

Paracetamol, also known as acetaminophen, was first made in 1878 by Harmon Northrop Morse or possibly 1852 by Charles Frédéric Gerhardt. It is a widely used medication for pain and fever.

Acetanilide was serendipitously found to possess analgesic and antipyretic properties, leading to its introduction into medical practice under the name of Antifebrin by Cahn & Hepp in 1886.

Paracetamol was first used clinically by von Mering in 1893.

In 1947, David Lester and Leon Greenberg found strong evidence that paracetamol was a major metabolite of acetanilide in human blood, leading to the rediscovery of paracetamol.

Bernard B. Brodie and Julius Axelrod published an article in 1948 titled 'The fate of acetanilide in man', which was a significant milestone in the history of paracetamol. The article played a crucial role in the rediscovery and rehabilitation of paracetamol as a popular over-the-counter painkiller.

Paracetamol appeared commercially in the United States in 1950.

In 1952, paracetamol returned to the US market as a prescription drug after reports of users stricken with agranulocytosis led to its temporary removal.

The Sterling-Winthrop Company started marketing Paracetamol under the name Panadol in 1953.

Acetaminophen, also known as paracetamol, was first marketed by McNeil Laboratories in 1955.

In 1956, Frederick Stearns & Co started selling a drug in the United Kingdom in 500-milligram tablets under the name Panadol, which later became popular and is now a household drug.

Until 1959, Paracetamol was only available by prescription, but it then became an over-the-counter medication.

In 1966, Davidson and Eastham reported a case of acute liver necrosis in a patient following an overdose of paracetamol. The study was published in the British Medical Journal.

In 1972, Flower and Vane explained that the inhibition of prostaglandin synthetase in the brain is responsible for the anti-pyretic activity of paracetamol, also known as 4-acetamidophenol.

The study conducted by Prescott in 1980 focused on the kinetics and metabolism of paracetamol and phenacetin.

In 1988, Sterling Winthrop was acquired by Eastman Kodak, which later sold the over-the-counter drug rights of paracetamol to SmithKline Beecham in 1994.

In 1995, a study investigated why patients opt for paracetamol in cases of self-poisoning and assessed their understanding of the risks associated with it.

Prescott's critical bibliographic review in 1996 delves into the comprehensive analysis of paracetamol (acetaminophen).

The PAIN Study conducted in 1999 was a large-scale, randomised clinical trial comparing the tolerability of aspirin, ibuprofen, and paracetamol for short-term analgesia.

The research by Rampal et al. in 2002 evaluated the gastrointestinal tolerability of ibuprofen in comparison to paracetamol and aspirin at over-the-counter doses.

AM404 was identified as a metabolite for paracetamol in 2005, which activates the endocannabinoid and TRPV1 systems, contributing to the analgesic action of paracetamol.

A study conducted in 2007 examined the impact of limiting the pack sizes of paracetamol on cases of paracetamol poisoning in the United Kingdom.

Rahme et al.'s study in 2008 examined hospitalizations for gastrointestinal events related to NSAIDs and acetaminophen among the elderly in Quebec, Canada.

In 2009, Bateman delivered the Louis Roche lecture in Stockholm, sharing his personal perspective on medicine, poison, and mystic potion, particularly focusing on paracetamol.

A study conducted in 2011 by Doherty et al. involved a randomised controlled trial comparing the efficacy of ibuprofen, paracetamol, and a combination tablet of ibuprofen/paracetamol in individuals with knee pain.

In 2013, De-Giorgio et al. documented a case of possible fatal acetaminophen intoxication with an atypical clinical presentation. The findings were published in the Journal of Forensic Sciences.

The study conducted in 2014 by Viberg, H., Eriksson, P., Gordh, T., Fredriksson, revealed that administration of Paracetamol during neonatal brain development can impact cognitive function and alter analgesic and anxiolytic responses in adult male mice.

As of 1 February 2018, medications containing codeine became prescription-only in Australia.

In 2021, Paracetamol was the 113th most commonly prescribed medication in the United States, with more than 5 million prescriptions. It is widely used for its analgesic and antipyretic properties.

A 2022 double-blind, placebo-controlled, crossover study found evidence that daily, high-dose use of paracetamol increases systolic blood pressure.