Shortly after Philip's murder, Alexander's longtime ally Antipater presented him to the Macedonian army, which immediately acclaimed Alexander king. The first matter Alexander attended to was the inevitable purging of enemies. This included potential claimants Amyntas and two sons of Aëropus (the third was spared because he was among the first to pay homage to Alexander, and also because he was the son-in-law of Antipater) who were known supporters of Amyntas. Many more murders would follow as necessity arose. Olympias showed her vengeful side in a gruesome murder of Caranus. However, while this killing was an order of Alexander, Olympias also murdered Caranus's sister and drove their mother, Cleopatra, to suicide. As Caranus's sister and mother posed no threat to the throne, Alexander was naturally furious at his mother, fearing the public scandal the murders might cause.

With the purging underway, Alexander still had to win the support of the Macedonian people and then attempt to maintain his hold over the foreign states. To assure his subjects, he publicly announced that he would run the state on the same principles as his father's administration; he even removed direct taxation on Macedonian citizens to win their appreciation.

The situation abroad, however, would be more complicated. Athens was thrilled to learn of Philip's death, seeing it as an opportunity to revolt. The famous Athenian orator Demosthenes immediately wrote to Attalus and Parmenion, one of Philip's most loyal lieutenants, to offer Athens's support and to urge them to declare war on Alexander. Although Attalus had to take this opportunity to save his own life, Alexander knew that Parmenion could be won over, and that success in doing so would greatly strengthen his power. While negotiations continued, Alexander took action against states that threatened to defect. Despite warnings against brashness, Alexander knew that he could not show any signs of weakness at this crucial moment. Therefore, he soon brought Thessaly and others into line, convincing them that cooperation would be the wisest decision.

Thebes presented a greater obstacle, as it was naturally averse to Macedonian rule. Alexander, however, offered such appealing terms as could not be refused–he simply asked to be recognized as Hegemon of the Hellenic League. Athens could not, at this point, hold out alone; soon its leaders were apologizing for the delay in acknowledging Alexander as king. Attalus himself gave in and tried to switch allegiances, but his efforts were futile, as Alexander's hatred was personal as well as political. When Attalus's life was the one point of dispute between Alexander and Parmenion–Attalus was Parmenion's son-in-law–Alexander remained firm, and he eventually got his way. With Parmenion's support, Alexander was able to reclaim–all without a battle, and in a short time–the status that his father had worked so hard to achieve.

His housecleaning and consolidation of power taken care of, Alexander soon turned his attention to reaffirming his rule over the barbarians. In these encounters, Alexander showed brilliant foresight and succeeded in near annihilations while losing very few men.

Meanwhile, trouble arose again in Thebes, as rebel leaders began stirring up anti-Macedonian feeling, particularly because of a rumor that Alexander had died. Though Alexander offered Thebes the chance to surrender when he arrived with 30,000 troops, the city, though shocked to see Alexander alive, was nevertheless determined to fight. For a while, the Thebans put up a valiant struggle outside the city walls. However, when Alexander found one gate left open and sent troops to rush in, the Thebans lost heart as their city was stormed.

What resulted was one of Alexander's most destructive massacres–6,000 Thebans killed, 30,000 taken prisoner; only 500 Macedonians lost. Furthermore, the victors did not hold back when the pillaging began. At the ensuing League meeting, the council voted to raze Thebes and sell the captured citizens as slaves. Though many representatives in the League had their own reason to hate Thebes, the destruction of the city still came as a shock to Greece, for Thebes had been one of the most historic and distinguished Greek city-states. Though Alexander successfully made an example of Thebes, he would never be forgiven for his lack of mercy on the city.