Callimachus was a man of Libyan Greek origin. He was born and raised in Cyrene, as member of a distinguished family, his parents being Mesatme (or Mesatma) and Battus, supposed descendant of the first Greek king of Cyrene, Battus I, through whom Callimachus claimed to be a descendant of the Battiad dynasty, the Libyan Greek monarchs that ruled Cyrenaica for eight generations and the first Greek Royal family to have reigned in Africa. He was named after his grandfather, an "elder" Callimachus, who was highly regarded by the Cyrenaean citizens and had served as a general.

Callimachus married the daughter of a Greek man called Euphrates who came from Syracuse. However, it is unknown if they had children. He also had a sister called Megatime but very little is known about her: she married a Cyrenaean man called Stasenorus or Stasenor to whom she bore a son, Callimachus (so called "the Younger" as to distinguish him from his maternal uncle), who also became a poet, author of "The Island".

In later years, he was educated in Athens. When he returned to North Africa, he moved to Alexandria.

Elitist and erudite, claiming to "abhor all common things," Callimachus is best known for his short poems and epigrams. During the Hellenistic period, a major trend in Greek-language poetry was to reject epic modelled after Homer. Instead, Callimachus urged poets to "drive their wagons on untrodden fields," rather than following in the well worn tracks of Homer, idealizing a form of poetry that was brief, yet carefully formed and worded, a style at which he excelled. In the prologue to his Aitia, he claims that Apollo visited him and admonished him to "fatten his flocks, but to keep his muse slender," a clear indication of his choice of carefully crafted and allusive material. "Big book, big evil" (???? ??????? ???? ?????, "mega biblion, mega kakon") is another of his verses, attacking long, old-fashioned poetry using the very style Callimachus proposed to replace it. Callimachus also wrote poems in praise of his royal patron and a wide variety of other poetic styles, as well as prose and criticism. Callimachus' most famous prose work is the Pinakes (Lists), a bibliographical survey of authors of the works held in the Library of Alexandria. It is said to have comprised 120 books.

Due to Callimachus' strong stance against the epic, he and his younger student Apollonius of Rhodes, who favored epic and wrote the Argonautica, had a long and bitter feud, trading barbed comments, insults, and ad hominem attacks for over thirty years. It is now known, through a papyrus fragment from Oxyrhynchus listing the earliest chief librarians of the Library of Alexandra, that Ptolemy II never offered the post to Callimachus, but passed him over for Apollonius Rhodius. Some classicists, including Peter Green, speculate that this contributed to the poets' long feud.

Though Callimachus was an opponent of "big books", the Suda puts his number of works at (a possibly exaggerated) 800, suggesting that he found large quantities of small works more acceptable. Of these, only six hymns, sixty-four epigrams, and some fragments are extant; a considerable fragment of the Hecale, one of Callimachus' few longer poems treating epic material, has also been discovered in the Rainer papyri. His Aitia ("Causes"), another rare longer work surviving only in tattered papyrus fragments and quotations in later authors, was a collection of elegiac poems in four books, dealing with the foundation of cities, obscure religious ceremonies, unique local traditions apparently chosen for their oddity, and other customs, throughout the Hellenic world In the first three books at least, the formula appears to ask a question of the Muse, of the form, "Why, on Paros, do worshippers of the Charites use neither flutes nor crowns?" "Why, at Argos is a month named for 'lambs'?" "Why, at Leucas, does the image of Artemis have a mortar on its head?" A series of questions can be reconstituted from the fragments. One passage of the Aitia, the so called Coma Berenices, has been reconstructed from papyrus remains and the celebrated Latin adaptation of Catullus (Catullus 66).

The extant hymns are extremely learned, and written in a style that some have criticised as labored and artificial. The epigrams are more widely respected, and several have been incorporated into the Greek Anthology.

According to Quintilian (10.1.58) he was the chief of the elegiac poets; his elegies were highly esteemed by the Romans (see Neoterics), and imitated by Ovid, Catullus, and especially Sextus Propertius. Many modern classicists hold Callimachus in high regard for his major influence on Latin poetry.

Callimachus was undoubtedly an authority on dogs in his day and his works shed light on the origins of the Maltese Dog as being sprawn from the island of Mljet (), which he placed near Kor?ula along the Dalmatian coast in the Adriatic Sea.