After the fulfilment of his military service as military tribune, Paullus was elected curule aedile in 193 BC. The next step of his cursus honorum was the election as praetor in 191 BC. At the term of this office he went to the Hispania provinces, where he campaigned against the Lusitanians between 191 and 189 BC. Paullus is elected consul for the first time in 182 BC, with Gnaeus Baebius Tamphilus as junior partner. His next military command, with proconsular imperium, was in the next year, against the Ingauni of Liguria.
The Third Macedonian War breaks in 171 BC, when king Perseus of Macedon defeats a Roman army led by the consul Publius Licinius Crassus in the battle of Callicinus. After two years of indecisive results for both sides, Paullus is elected consul again in 168 BC (with Gaius Licinius Crassus as colleague). As consul, he is appointed by the senate to deal with the Macedonian war. Shortly afterwards, in June 22, he wins the decisive battle of Pydna. Perseus of Macedonia is made prisoner and the Third Macedonian War ends.
To set an example, Paullus ordered the killing of 500 Macedonians known for opposition against Rome. He also exiled many more to Italy and confiscated his belongings in the name of Rome but according to Plutarch, keeping too much to himself. On the return to Rome in 167 BC, his legions were displeased with their share of the plunder. To keep them happy, Paullus decided for a stop in Epirus, a kingdom under accusations of sympathizing with the Macedonian cause. The region had been already pacified, but Paullus ordered the sacking of 70 its towns. 150,000 people were enslaved and the region was left to bankruptcy.
Paullus return to Rome was glorious. With and immense plunder collected in Macedonia and Epirus, he celebrated a spectacular triumph, featuring no less than the captured king of Macedonia himself. As a gesture of acknowledgment, the senate awards him the surname Macedonicus. This was the peak of his career. In 164 BC he his elected censor and dies during his term in 160 BC.
With the death of Macedonicus, the Aemilii Paullii ended too. The successes of his political and military career were not accompanied by a happy family life. He had been married to Papiria Masonis, from whom he divorced, according to Plutarch, for no particular reason. From this marriage four children were born: two boys and two Aemilias, one married to the son of Cato the elder, another to Aelius Tubero, a rich man of a plebeian family. Paullus Macedonicus then married a second time and had two sons. Since four boys were too many for a father to support across the cursus honorum, he decided to give the oldest two for adoption. One was taken by Fabius Maximus and became Quintus Fabius Maximus Aemilianus. The other was adopted by Publius Cornelius Scipio, son of Scipio Africanus, and became Scipio Aemilianus|Publius Cornelius Scipio Aemilianus, known as Scipio Africanus the Younger, following his conquest of Carthage in the Third Punic War in 146 BC. With the oldest sons safely adopted by two of the most powerful patrician houses, Paullus Macedonicus counted on the two younger ones to continue his own name. This was not due to happen. Both of them died young, one shortly after the other, at the same time that Paullus celebrated his triumph.