Manuel's death on 24 September 1180, marked a turning point in the fortunes of the Byzantine Empire. Andronikos began his reign well. in particular, the measures he took to reform the government of the empire have been praised by historians. In the provinces, Andronikos' reforms produced a speedy and marked improvement. Andronikos's fierce determination to root out corruption and many other abuses was admirable; under Andronikos, the sale of offices ceased; selection was based on merit, rather than favouritism; officials were paid an adequate salary so as to reduce the temptation of bribery. Every form of corruption was eliminated with ferocious zeal.

There were several revolts, leading to an invasion by King William II of Sicily. Andronikos hastily assembled five different armies to stop the Sicilian army from reaching Constantinople, but his forces failed to stand and retreated to the outlying hills. Andronikos also assembled a fleet of 100 ships to stop the Norman fleet from entering the Sea of Marmara.

When Andronikos returned to Constantinople, he found that his authority was overthrown: Isaac Angelos had been proclaimed emperor. The deposed Emperor attempted to escape in a boat with his wife Agnes and his mistress, but was captured. Isaac handed him over to the city mob and for three days he was exposed to their fury and resentment. His right hand was cut off, his teeth and hair were pulled out, one of his eyes was gouged out, and, among many other sufferings, boiling water was thrown in his face. He died on September 12, 1185. At the news of the emperor's death, his son and co-emperor, John, was murdered by his own troops in Thrace.