One Megacles was the archon eponymous in 632 BC when Cylon made his unsuccessful attempt to take over Athens. Megacles was convicted of killing Cylon (who had taken refuge on the Acropolis as a suppliant of Athena) and was exiled from the city, along with all the other members of his genos, the Alcmaeonidae. The Alcmaeonidae inherited a miasma ("stain") that lasted for generations among Megacles' descendants.
Another Megacles, the grandson of the above, was an opponent of Pisistratus in the 6th century BC. He drove out Pisistratus during the latter's first reign as tyrant in 560 BC, but the two then made an alliance with each other, and Pisistratus married Megacles' daughter. They also tricked the Athenians into believing Athena herself had arrived to proclaim Pisistratus tyrant, by dressing up a woman named Phye as the goddess. However, Megacles turned against Pisistratus when Pisistratus refused to have children with Megacles' daughter, thus ending the second tyranny.
The latter Megacles competed with Hippocleides to marry to Agarista, the daughter of Cleisthenes of Sicyon. His son with Agarista, also named Megacles, was the grandfather of yet another Megacles, who himself was the uncle of Pericles.
A much earlier Megacles was a (possibly legendary) King of Athens from 922 BC to 892 BC.