Paracelsus' mother probably died in 1502, after which Paracelsus' father moved to Villach, Carinthia where he worked as a physician, attending to the medical needs of the pilgrims and inhabitants of the cloister. Paracelsus was educated by his father in botany, Medicine, mineralogy, mining, and natural philosophy. He also received a profound humanistic and theological education from local clerics and the convent school of St. Paul's Abbey in the Lavanttal. He specifically accounts for being tutored by Johannes Trithemius, abbot of Sponheim. At the age of 16 he started studying Medicine at the University of Basel, later moving to Vienna. He gained his doctorate degree from the University of Ferrara in 1515 or 1516.

Between 1517 and 1524, he worked as a military surgeon, in Venetian Service in 1522. In this capacity he travelled widely across Europe, and possibly as far as Constantinople.

He settled in Salzburg in 1524 but had to leave in the following year due to his support of the German Peasants' War. In 1525, he was active at the University of Freiburg.

He was probably the first to give the element zinc (zincum) its modern name, in about 1526, likely based on the sharp pointed appearance of its crystals after smelting (zinke translating to "pointed" in German). Paracelsus invented chemical therapy, chemical urinalysis, and suggested a biochemical theory of digestion. Paracelsus used chemistry and chemical analogies in his teachings to medical students and to the medical establishment, many of whom found them objectionable.

In 1527, Paracelsus was a licensed physician in Basel with the privilege of lecturing at the University of Basel. Basel at the time was a center of Renaissance humanism, and Paracelsus here came into contact with Erasmus of Rotterdam, Wolfgang Lachner, and Johannes Oekolampad. Paracelsus' lectures at Basel university unusually were held in German, not Latin. He stated that he wanted his lectures to be available to everyone. He also published harsh criticism of the Basel Physicians and apothecaries, creating political turmoil to the point of his life being threatened. In a display of his contempt for conventional Medicine, Paracelsus publicly burned editions of the works of Galen and Avicenna. He was prone to many outbursts of abusive language, abhorred untested theory, and ridiculed anybody who placed more importance on titles than practice ('if disease put us to the test, all our splendor, title, ring, and name will be as much help as a horse's tail'). During his time as a professor at the University of Basel, he invited barber-surgeons, alchemists, apothecaries, and others lacking academic background to serve as examples of his belief that only those who practiced an art knew it: 'The patients are your textbook, the sickbed is your study.' Paracelsus was compared with Martin Luther because of his openly defiant acts against the existing authorities in Medicine. Paracelsus rejected that comparison. Famously Paracelsus said, "I leave it to Luther to defend what he says and I will be responsible for what I say. That which you wish to Luther, you wish also to me: You wish us both in the fire." Being threatened with an unwinnable lawsuit, he left Basel for Alsace in February 1528.

In Alsace, Paracelsus took up the life of an itinerant physician once again. After staying in Colmar with Lorenz Fries (de), and briefly in Esslingen, he moved to Nuremberg in 1529. His reputation went before him, and the medical professionals excluded him from practicing.

Paracelsus was one of the first medical professors to recognize that Physicians required a solid academic knowledge in the natural sciences, especially chemistry. Paracelsus pioneered the use of chemicals and minerals in Medicine. From his study of the elements, Paracelsus adopted the idea of tripartite alternatives to explain the nature of Medicine, taking the place of a combustible element (sulphur), a fluid and changeable element (mercury), and a solid, permanent element (salt). The first mention of the mercury-sulphur-salt model was in the Opus paramirum dating to about 1530. Paracelsus believed that the principles sulphur, mercury, and salt contained the poisons contributing to all diseases. He saw each disease as having three separate cures depending on how it was afflicted, either being caused by the poisoning of sulphur, mercury, or salt. Paracelsus drew the importance of sulphur, salt, and mercury from medieval alchemy, where they all occupied a prominent place. He demonstrated his theory by burning a piece of wood. The fire was the work of sulphur, the smoke was mercury, and the residual ash was salt. Paracelsus also believed that mercury, sulphur, and salt provided a good explanation for the nature of Medicine because each of these properties existed in many physical forms. The tria prima also defined the human identity. Salt represented the body; mercury represented the spirit (imagination, moral judgment, and the higher mental faculties); sulfur represented the soul (the emotions and desires). By understanding the chemical nature of the tria prima, a physician could discover the means of curing disease. With every disease, the symptoms depended on which of the three principals caused the ailment. Paracelsus theorized that materials which are poisonous in large doses may be curative in small doses; he demonstrated this with the examples of magnetism and static electricity, wherein a small magnet can attract much larger metals.

His Astronomia magna (also known as Philosophia sagax) was completed in 1537, but published only in 1571. It is a treatise on hermeticism, astrology, divination, theology, and demonology, and it laid the basis of Paracelsus' later fame as a "prophet". His motto Alterius non sit qui suus esse potest ("Let no man belong to another who can belong to himself") is inscribed on a 1538 portrait by Augustin Hirschvogel.

The oldest surviving portrait Paracelsus is a woodcut by Augustin Hirschvogel, published in 1538, still during Paracelsus' lifetime. A still older painting by Quentin Matsys has been lost, but at least three 17th-century copies survive, one by an anonymous Flemish Artist, kept in the Louvre, one by Peter Paul Rubens, kept in Brussels, and one by a student of Rubens', now kept in Uppsala. Another portrait by Hirschvogel, dated 1540, claims to show Paracelsus "at the age of 47" (sue aetatis 47), i.e. less than a year before his death. In this portrait, Paracelsus is shown as holding his sword, gripping the spherical pommel with the right hand. Above and below the image are the mottos Alterius non sit qui suus esse potest ("Let no man belong to another who can belong to himself") and Omne donum perfectum a Deo, inperfectum a Diabolo ("All perfect gifts are from God, [all] imperfect [ones] from the Devil"); later portraits give a German rendition in two rhyming couplets (Eines andern Knecht soll Niemand sein / der für sich bleiben kann allein /all gute Gaben sint von Got / des Teufels aber sein Spot). Posthumous portraits of Paracelsus, made for publications of his books during the second half of the 16th century, often show him in the same pose, holding his sword by its pommel.

In 1541, Paracelsus moved to Salzburg, probably on the invitation of Ernest of Bavaria, where he died on 24 September. He was buried in St Sebastian cemetery in Salzburg. His remains were relocated inside St Sebastian church in 1752.

Paracelsus was especially venerated by German Rosicrucians, who regarded him as a prophet, and developed a field of systematic study of his writings, which is sometimes called "Paracelsianism", or more rarely "Paracelsism". Francis Bacon warned against Paracelsus and the Rosicrucians, judging that "the ancient opinion that man was microcosmus" had been "fantastically strained by Paracelsus and the alchemists". "Paracelsism" also produced the first complete edition of Paracelsus' works. Johannes Huser of Basel (c. 1545–1604) gathered autographs and manuscript copies, and prepared an edition in ten volumes during 1589–1591.

In the so-called "Rosicrucian portrait", published with Philosophiae magnae Paracelsi (Heirs of Arnold Birckmann, Cologne, 1567), is closely based on the 1540 portrait by Hirschvogel (but mirrored, so that now Paracelsus' left hand rests on the sword pommel), adding a variety of additional elements: the pommel of the sword is inscribed by Azoth, and next to the figure of Paracelsus, the Bombast von Hohenheim arms are shown (with an additional border of eight crosses patty). Shown in the background are "early Rosicrucian symbols", including the head of a child protruding from the ground (indicating rebirth). The portrait is possibly a work by Frans Hogenberg, acting under the directions of Theodor Birckmann (1531/33–1586)

After his death, the movement of Paracelsianism was seized upon by many wishing to subvert the traditional Galenic physics, and his therapies became more widely known and used. His autographs have been lost, but fortunately many of his works which remained unpublished during his lifetime were edited by Johannes Huser of Basel during 1589–1591. His works were frequently reprinted and widely read during the late 16th to early 17th century, and although his "occult" reputation remained controversial, his medical contributions were universally recognized, with e.g. a 1618 pharmacopeia by the Royal College of Physicians in London including "Paracelsian" remedies.

He also had a substantial impact as a prophet or diviner, his "Prognostications" being studied by Rosicrucians in the 1700s. Paracelsianism is the early modern medical movement inspired by the study of his works.

Paracelsus was born in Egg, a village close to the Etzel Pass in Einsiedeln, Schwyz. He was born in a house right next to a bridge across the Sihl river (known as Teufelsbrücke). The historical house, dated to the 14th century, was destroyed in 1814. The Restaurant Krone now stands in its place. His father Wilhelm (d. 1534) was a Chemist and physician, an illegitimate descendant of the Swabian noble family Bombast von Hohenheim. It has been suggested that Paracelsus' descent from the Bombast of Hohenheim family was his own invention, and that his father was in fact called Höhener and was a native of Gais in Appenzell, but it is plausible that Wilhelm was the illegitimate son of Georg Bombast von Hohenheim (1453–1499), commander of the Order of Saint John in Rohrdorf.

A number of fictionalised depictions of Paracelsus have been published in modern literature. The first presentation of Paracelsus' life in the form of a historical novel was published in 1830 by Dioclès Fabre d'Olivet (1811–1848, son of Antoine Fabre d'Olivet), Robert Browning wrote a long poem based on the life of Paracelsus, entitled Paracelsus, published 1835. Meinrad Lienert in 1915 published a tale (which he attributed to Gall Morel) about Paracelsus' sword. Arthur Schnitzler wrote a verse play Paracelsus in 1899. Erwin Guido Kolbenheyer wrote a novel trilogy (Paracelsus-Trilogie), published during 1917–26.

Hippocrates put forward the theory that illness was caused by an imbalance of the four humors: blood, phlegm, black bile and yellow bile. These ideas were further developed by Galen into an extremely influential and highly persistent set of medical beliefs that were to last until the mid-1850s. Contrarily, Paracelsus believed in three humors: salt (representing stability), sulfur (representing combustibility), and mercury (representing liquidity); he defined disease as a separation of one humor from the other two. He believed that body organs functioned alchemically, that is, they separated pure from impure. The dominant medical treatments in Paracelsus' time were specific diets to help in the "cleansing of the putrefied juices" combined with purging and bloodletting to restore the balance of the four humors. Paracelsus supplemented and challenged this view with his beliefs that illness was the result of the body being attacked by outside agents. He objected to excessive bloodletting, saying that the process disturbed the harmony of the system, and that blood could not be purified by lessening its quantity.

Martha Sills-Fuchs (1896–1987) wrote three völkisch plays with Paracelsus as the main character during 1936–1939 in which Paracelsus is depicted as the prophetic healer of the German people. The German drama film Paracelsus was made in 1943, directed by Georg Wilhelm Pabst. Also in 1943, Richard Billinger wrote a play Paracelsus for the Salzburg Festival. Mika Waltari's Mikael Karvajalka (1948) has a scene fictionalising Paracelsus' acquisition of his legendary executioner's sword. Paracelsus is the main character of Jorge Luis Borges's short story La rosa de Paracelso (anthologized 1983). An Alchemist based on him named Van Hohenheim is one of the main characters of the manga Fullmetal Alchemist. The Rose of Paracelsus: On Secrets and Sacraments, borrowing from Jorge Luis Borges, is also a novel by william Leonard Pickard.

The name Paracelsus is first attested in this year, used as "pseudonym" for the publication of a Practica of political-astrological character in Nuremberg. Pagel (1982) supposes that the name was intended for use as the author of non-medical works, while his real name Theophrastus von Hohenheim was used for medical publications. The first use of Doctor Paracelsus in a medical publication was in 1536, as the author of the Grosse Wundartznei. The name is usually interpreted as either a latinization of Hohenheim (based on celsus "high, tall") or as the claim of "surpassing Celsus". It has been argued that the name was not the invention of Paracelsus himself, who would have been opposed to the humanistic fashion of Latinized names, but was given to him by his circle of friends in Colmar in 1528. It is difficult to interpret but does appear to express the "paradoxical" character of the man, the prefix "para" suggestively being echoed in the titles of Paracelsus' main philosophical works, Paragranum and Paramirum (as it were "beyond the grain" and "beyond wonder"); a paramiric treatise having been announced by Paracelsus as early as 1520.

As a physician of the early 16th century, Paracelsus held a natural affinity with the Hermetic, Neoplatonic, and Pythagorean philosophies central to the Renaissance, a world-view exemplified by Marsilio Ficino and Pico della Mirandola. Paracelsus rejected the magic theories of Heinrich Cornelius Agrippa and Nicolas Flamel in his Archidoxes of Magic. Astrology was a very important part of Paracelsus' Medicine and he was a practicing astrologer – as were many of the university-trained Physicians working at that time in Europe. Paracelsus devoted several sections in his writings to the construction of astrological talismans for curing disease. He also invented an alphabet called the Alphabet of the Magi, for engraving Angelic names upon talismans. Paracelsus largely rejected the philosophies of Aristotle and Galen, as well as the theory of humours. Although he did accept the concept of the four elements as water, air, fire, and earth, he saw them merely as a foundation for other properties on which to build.

The late 16th century also saw substantial production of Pseudo-Paracelsian writing, especially letters attributed to Paracelsus, to the point where biographers find it impossible to draw a clear line between genuine tradition and legend.

The prophecies contained in Paracelsus' works on astrology and divination began to be separately edited as Prognosticon Theophrasti Paracelsi in the early 17th century. His prediction of a "great calamity just beginning" indicating the End Times was later associated with the Thirty Years' War, and the identification of Gustavus Adolphus of Sweden as the "Lion from the North" is based in one of Paracelsus' "prognostications" referencing Jeremiah 5:6.

During Paracelsus's lifetime and after his death, he was often celebrated as a wonder healer and investigator of those folk medicines that were rejected by the fathers of Medicine (e.g. Galen, Avicenna). It was believed that he had success with his own remedies curing the plague, according to those that revered him. Since effective medicines for serious infectious diseases weren't invented before the 19th century, Paracelsus came up with many prescriptions and concoctions on his own. For infectious diseases with fever, it was Common to prescribe diaphoretics and tonics that at least gave temporary relief. Also many of his remedies contained the famed "theriac", a preparation derived from oriental Medicine sometimes containing opium. The following prescription by Paracelsus was dedicated to the village of Sterzing.