Themis, the Titaness of justice and another of Zeus's consorts reared Apollo and Artemis, who both excelled in various disciplines and activities. Apollo became a master archer under the tutelage of his uncle, the centaur Chiron and he also became familiar with the musical arts.

Apollo was widely revered for his defeat of the monstrous serpent Python in the land of Delphi, formerly called Pytho. Other than harassing Leto when she was pregnant with Apollo and Artemis, Python was responsible for widespread destruction and environmental problems in Delphi. Apollo slew Python with his bow and arrows and thereafter took charge of the oracle that resided at Delphi whom Themis was formerly the patroness of. Delphi became the most important oracle center of Apollo.

Apollo, as with Zeus his father, engaged in many affairs with goddesses and mortals and sired several offspring by them as well. His children were both mortal and immortal respectively. With Iris, goddess of the rainbow, he sired the god Janus who was regarded as a guardian-deity to the Roman peoples. Apollo once loved the goddess-nymph Cyrene and by her fathered the god Aristaeus. Both he and his half-brother Hermes, the speedster-god mated with the mortal Chione who bore Hermes Autolycus and to Apollo, Philammon. One of Apollo's most famous mortal lovers was Queen Hecuba, the wife of Priam, the last king of Troy. By Hecuba, he fathered Troilius whose death at the hands of the demi-god Achilles foreshadowed the defeat of Troy. Apollo also fell in love with Cassandra, the half-sister of his son Troilius, and the daughter of Hecuba and Priam. He seduced Cassandra on the promise that he would bestow her with precognitive powers. When he imbued her with the ability, Cassandra rejected his amorous advances. Apollo, enraged, punished Cassandra, by declaring her prophecies would never be believed by anyone. Indeed, Cassandra foresaw the destruction of Troy by the Greek warriors but was never believed when she told others of her prophetic visions.

Asclepius was also Apollo's offspring from his union with Coronis, the daughter of Phlegyas, King of the Lapiths. Upon the death of Asclepius's mother while he was still a babe, Apollo gave the boy to his uncle, the centaur Chiron to be raised. Chiron was the youngest son of the Titan Cronus, Apollo's paternal grandfather. Asclepius was Apollo's most famous son because of his medicinal skills which even enabled him to raise the dead. The god of the dead Hades, however, complained to Zeus of this matter resulting in Zeus killing Asclepius with one of his thunderbolts. Angered by his son's death and not able to lash out at his own father, Apollo turned his anger on the Cyclopes who had trained Zeus in the use of his lightning bolts. As punishment Zeus made Apollo a mortal and made him serve King Admetus of Pherae for nearly a decade. Resultingly, Apollo befriended Admetus and warned him of his impending death. Admetus' wife, Alcestis sacrificed herself in her husband's place when the god of death, Thannatos came to escort him to the underworld. Alcestis was saved by the demigod Hercules' intervention. Apollo eventually regained his godhood and returned to Olympus. Apollo eventually petitioned Zeus to resurrect Asclepius and transform him into a full Olympian and thus Asclepius became the god of medicine.

Apollo was also capable of great cruelty when he was angered. He deceived his sister Artemis into accidentally killing their cousin, the giant Orion and a son of Poseidon who had fallen in love with Artemis. Apollo also slew the giant Tityus with his sister and when the mortal woman, Queen Niobe of Thebes, boasted to Apollo's mother Leto, that she had borne fourteen children and thus was superior to the goddess since she only bore two, Apollo and Artemis were greatly angered and with their bows and arrows slew Niobe's children. Artemis slew the daughters and Apollo slew the sons.

(Thor Annual#5) - When Hercules attempted to convince Zeus to wage war against Asgard, Apollo was among the gods who opposed the conflict.

(Doctor Strange II#46 (fb)) - Two thousand years ago, the seeress named Sibylla came to the temple of Apollo and Artemis at Mt. Gaurus, and Apollo made her his oracle. When Sibylla's mortal life came to an end, Apollo offered her a place in Olympus, but she declined, wanting to watch over her successors as a spirit. The Sibylline Sisterhood was broken when Thaleia was driven insane and killed herself, but Apollo sealed Thaleia's soul within her body and placed it into suspended animation, so that Thaleia might one day redeem herself.

(Venus#1/2) - Apollo tended to Venus after she returned from a visit to Earth.

(Venus#3/4) - Apollo later followed Venus to Earth and took the name of "Paul Belvedere" to interact with mortals, but when his visit resulted in the sun's refusal to set, Venus led him back to Olympus and commanded him to remain.

(Venus#5) - Zeus sent Apollo and Daphne to Earth under the aliases of "Renee Andre" and "Rona Belladonna" to break up Meg Saunders and her boyfriend Danny so that Venus would be forced to leave Earth, but Venus saw through their efforts and helped Meg and Danny stay together, earning Zeus' permission to remain on Earth.

(Venus#10 - BTS) - When the villainous Son of Satan threatened the earth with catastrophes, Venus called upon Apollo to end a flood he had caused, and later had him imprison the Son of Satan within a disc of flame, and sent him hurtling into space.

(Thor: Blood Oath#3-4) - Apollo observed Hercules and Thor as they fought over the enchanted pig of Dionysus.

(Avengers I#50) - Apollo was among those Olympians banished to the Land of Shades by Typhon. With the defeat of Typhon by Hercules, Apollo was released.