The first notable Alcmaeonid was Megacles, who was archon eponymous of Athens in the 7th century BC. He was responsible for killing Cylon and Cylon's followers during the attempted coup of 632 BC. As Cylon had taken refuge as a suppliant at the temple of Athena, Megacles and his Alcmaeonid followers inherited a curse and were exiled from the city. Even the bodies of buried Alcmaeonidae were dug up and removed from the city limits.
The Alcmaeonids were allowed back into the city in 594 BC, during the reign of Solon. During the tyranny of Pisistratus, the Alcmaeonid Megacles married his daughter to Pisistratus, but when the tyrant refused to have children with her Megacles banished him. When Pisistratus returned for his third tyranny in 538 BC, the Alcmaeonids were exiled once more. Nevertheless their reputation remained high, and Megacles was able to marry Agarista, the daughter of Cleisthenes of Sicyon, from whom the Athenian reformer also named Cleisthenes was descended.
This Cleisthenes overthrew Hippias, the son and successor of Pisistratus, in 508 BC. He had bribed the oracle at Delphi (which the Alcmaeonidae had helped to build while they were in exile) to convince the Spartans to help him, which they reluctantly did. Cleisthenes was, at first, opposed by some who felt the curse made the Alcmaeonidae ineligible to rule; the Spartan king Cleomenes I even turned against Cleisthenes and the latter was briefly exiled once more. However, the citizens called for Cleisthenes to return, and the restored Alcmaeonids were responsible for laying the foundations of Athenian democracy.
The Alcmaeonidae were said to have negotiated for an alliance with the Persians during the Persian Wars, despite the fact that Athens was leading the resistance to the Persian invasion. Pericles and Alcibiades were also Alcmaeonidae, and during the Peloponnesian War the Spartans referred to the family curse in an attempt to discredit Pericles. Alcibiades, as the previous generation of Alcmaeonidae had done, tried to ally with the Persians after he was accused of impiety. The family disappeared after Athens defeat in the Peloponnesian War.