Very little is known about Lucretius's life; the only certain fact is that he was either a friend or a client of Gaius Memmius, to whom he dedicated De Rerum Natura.

Another piece of information is found in a letter Cicero wrote to his brother Quintus in February 54 BCE. Cicero writes: "The poems of Lucretius are as you write: they exhibit many flashes of genius, and yet show great mastership." Apparently, by February 54 BCE both Cicero and his brother had read De Rerum Natura. However, internal evidence from the poem suggests that it was published without a final revision, possibly due to its author's untimely death. If this is true, Lucretius must have been dead by February 54 BCE.

Virgil writes in the second book of his Georgics, clearly referencing Lucretius, "Happy is he who has discovered the causes of things and has cast beneath his feet [subiecit pedibus; cf. Lucretius 1.78, religio pedibus subiecta, "religion lies cast beneath our feet"] all fears, unavoidable fate, and the din of the devouring Underworld."

A brief biographical notice is found in Aelius Donatus's Life of Virgil, which seems to be derived from an earlier work by Suetonius. The statement runs as follows: "The first years of his life Virgil spent in Cremona, right until the assumption of his toga virilis, which he accepted on his 17th birthday, when the same two men held the consulate, as when he was born, and it so happened that on the very same day Lucretius the poet passed away." The information in this testimony is internally inconsistent. Virgil was born in 70 BCE, and his 17th birthday therefore took place in 53 BCE. However, the two consuls of 70 BCE, Pompey and Crassus, stood together as consuls again in 55, not 53. So which year should we take as the year of Lucretius's death?

A yet more brief notice is found in the Chronicon of Donatus's pupil, Jerome. Writing 4 centuries after Lucretius's death, he enters under the 171st Olympiad, the following line: "Titus Lucretius the poet is born. Later he was driven mad by a love potion, and when, during the intervals of his insanity, he had written a number of books, which were later emended by Cicero, he killed himself by his own hand in the 44th year of his life." The claim that he was driven mad by a love potion, although defended by some, is often dismissed as the result of historical confusion, or anti-Epicurean slander. Similarly, the statement that Cicero emended () the work prior to publication is doubtful. The exact date of his birth varies by manuscript; in most it is tallied under 94 BCE, but in others under 93 or 96.

It is impossible to know how credible the accounts of Donatus and Jerome are, since they wrote long after the poet's death and we do not know the sources of their off-hand comments. However, if we have to pick one of the dates mentioned above, 55 BCE would be Lucretius's most likely year of death, and if Jerome is accurate about Lucretius's age (43) when he died, we can then conclude he was born in 99 or 98 BCE. These are a lot of ifs, and it may be wisest to simply say that Lucretius was born in the 90s and died in the 50s BCE. This ties in well with the poem's many allusions to the tumultuous state of political affairs in Rome and its civil strife.

According to Lucretius's frequent statements in his poem, the main purpose of the work was to free Gaius Memmius's (and presumably all of mankind's) mind of superstition and the fear of death. He attempts this by expounding the philosophical system of Epicurus, whom Lucretius apotheosizes as the hero of his epic poem.

Lucretius identifies superstition (religio in the Latin) with the notion that the gods/supernatural powers created our world or interfere with its operations in any way. He argues against fear of such gods by demonstrating through observations and logical argument that the operations of the world can be accounted for entirely in terms of natural phenomena...the regular but purposeless motions and interactions of tiny atoms in empty space...instead of in terms of the will of the gods.

He argues against the fear of death by stating that death is the dissipation of a being's material mind. Lucretius uses the analogy of a vessel, stating that the physical body is the vessel that holds both the mind (mens) and spirit (anima) of a human being. Neither the mind nor spirit can survive independent of the body. Thus Lucretius states that once the vessel (the body) shatters (dies) its contents (mind and spirit) can, logically, no longer exist. So, as a simple ceasing-to-be, death can be neither good nor bad for this being. Being completely devoid of sensation and thought, a dead person cannot miss being alive. According to Lucretius, fear of death is a projection of terrors experienced in life, of pain that only a living (intact) mind can feel. Lucretius also puts forward the 'symmetry argument' against the fear of death. In it, he says that people who fear the prospect of eternal non-existence after death should think back to the eternity of non-existence before their birth, which they probably do not fear.

The structure of the poem over the six books falls into two main parts. The first three books provide a fundamental account of being and nothingness, matter and space, the atoms and their movement, the infinity of the universe both as regards time and space, the regularity of reproduction (no prodigies, everything in its proper habitat), the nature of mind (animus, directing thought) and spirit (anima, sentience) as material bodily entities, and their mortality, since they and their functions (consciousness, pain) end with the bodies that contain them and with which they are interwoven. The last three books give an atomic and materialist explanation of phenomena preoccupying human reflection, such as vision and the senses, sex and reproduction, natural forces and agriculture, the heavens, and disease.

His poem De Rerum Natura (usually translated as"On the Nature of Things" or "On the Nature of the Universe") transmits the ideas of Epicurean physics, which includes Atomism, and psychology. Lucretius was one of the first Epicureans to write in Latin.

Lucretius compares his work in this poem to that of a doctor healing a child: just as the doctor may put honey on the rim of a cup containing bitter wormwood (most likely Absinth Wormwood) believed to have healing properties, the patient is "tricked" into accepting something beneficial but difficult to swallow, "but not deceived" by the doctor (Book IV lines 12-19). The meaning of this refrain found throughout the poem is debatable.

Stylistically, most scholars attribute the full blossoming of Latin hexameter to Virgil. De Rerum Natura however, is of indisputable importance for the part it played in naturalizing Greek philosophical ideas and discourse in the Latin language and its influence on Virgil and other later poets. Lucretius's hexameter is very distinct from the smooth urbanity of Virgil or Ovid. His use of heterodyne, assonance, and vigorously syncopated Latin forms create a harsh acoustic to some ears, although this is probably merely an impression created by contrast with later poets and general unfamiliarity with Latin poetry recited by skilled readers. John Donne has a similar reputation in English poetry because of his powerful and thought-laden discourse. The sustained energy of Lucretius's poetry (even when treating highly technical particularities, such as the movement of atoms through space or the films which give rise to vision when they strike the eye) is virtually unparalleled in Latin literature, with the possible exception of parts of Tacitus's Annals, or perhaps Books II and IV of the Aeneid. The six books contain many formulaic elements such as deliberately repeated lines, refrains, and regularized emotional peaks.

Among many poetic high points a few should be mentioned. The introduction to Book I (the invocation to Venus and Spring) is unsurpassed, both in its initial ecstatic address to the life-force and regeneration, and in the celebration of the courage and clear-sightedness of Epicurus and the vitriolic polemic against superstition (Latin: "religio") which provide the bridge to the main didactic body of the poem. The opening sections of the various books emphasize the novelty of the undertaking Lucretius has set himself and the gratitude mankind owes to Epicurus for delivering it from unfounded terrors and an empty, joyless and servile life. And the great conclusions to Book III (on death and why it holds no terrors) and Book VI (on disease, especially the plague) are as graphic as anything in literature, as are various accounts throughout the poem of storms, battles, fire and flood.

Cornelius Nepos, in his Life Of Atticus, mentions Lucretius as one of the greatest poets of his times.

Ovid, in his Amores, writes: Carmina sublimis tunc sunt peritura Lucreti / exitio terras cum dabit una dies (which means the verses of the sublime Lucretius will perish only when a day will bring the end of the world).

Vitruvius (in the De Architectura), Quintilian (in his Institutiones Oratoriae) and Statius (in the Silvae) also show great admiration for the De Rerum Natura.

Michel de Montaigne, in one of his Essays, On Books, lists Lucretius among Virgil, Horace, and Catullus as his four top poets.

Lucretius has also had a marked influence upon modern philosophy, as perhaps the most complete expositor of Epicurean thought. His influence is especially notable in Spanish-American philosopher George Santayana, who praised Lucretius (along with Dante and Goethe) in his book 'Three Philosophical Poets.'