The great betrayal/betrayer

Order 66 (star wars): after secretly starting a war to obtain unchecked power over the Galactic Republic, Darth sideous gives order 66, the execution of all Jedi and solidifies the creation of the Empire .

The Horus Heresy (Warhammer 40k (although this takes place in 30k)): half of the emperor of mankind's demigod sons fall to chaotic corruption, doubt, and their worst natures, and led by Horus Lupercal, wage a civil war that leaves the imperium a broken husk for millennia to come.

The Amaris Coup (Battletech/MechWarrior): Generations of scheming by House Amaris results in Stefan Amaris befriending the future first lord of star league, and practically raising him to adulthood into the perfect fool to assassinate and usurp. Through this, he gained control of the most powerful nation since mankind took to the stars, and while the Star League loyalists led by Aleksandr Kerensky would remove him from power in a brutal civil war, his extermination of house Cameron ensured the star league would never truly recover.

The assassination of Julius Caesar (History/Shakespeare): after Caesar's many victories, honors, and unprecedented political powers, a number of politicians, notably Brutus and Cassius, became worried that he was going make himself king. Though he rebuffed attempts by his supporters to give him a crown or to address him as king, the conspirators lured him to the Senate and stabbed him to death.