His father was Lucius Aemilius Paullus, the consul defeated and killed in the battle of Cannae. Lucius Aemilius was, in his time, the head of his branch of the Aemilii Pauli, an old and aristocratic patrician family. Their influence was immense, particularly due to their fortune and alliance with the Cornelii Scipiones. He was father to Scipio Aemilianus Africanus
 Early career After the fulfilment of his military service, and being elected 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. However, he failed to be elected consul for several years. Paullus was 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.
 Paullus and Macedonia The Third Macedonian War broke out in 171 BC, when king Perseus of Macedon defeated a Roman army led by the consul Publius Licinius Crassus in the battle of Callicinus. After two years of indecisive results for both sides, Paulus was elected consul again in 168 BC (with Gaius Licinius Crassus as colleague). As consul, he was appointed by the senate to deal with the Macedonian war. Shortly afterwards, in June 22, he won the decisive battle of Pydna. Perseus of Macedonia was made prisoner and the Third Macedonian War ended.
To set an example, Paulus ordered the killing of 500 Macedonians known for opposition against Rome. He also exiled many more to Italy and confiscated their 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, Paulus decided for a stop in Epirus, a kingdom suspected of sympathizing with the Macedonian cause. The region had been already pacified, but Paulus ordered the sacking of 70 of its towns. 150,000 people were enslaved and the region was left to bankruptcy.
Paulus' return to Rome was glorious. With the 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 awarded him the surname Macedonicus. This was the peak of his career. In 164 BC he was elected censor. He fell ill, appeared to be recovering, but relapsed within three days and died during his term in 160 BC.
 Family life and descendants His father Lucius Aemilius Paullus died in battle in 216 BC in the Battle of Cannae, while Aemilius Paullus must have been a very young man. The Aemilii Paulli were connected by marriage and political interests to the Scipios, but their role in his subsequent upbringing is not clear.
He had been married first to Papiria Masonis (or Papiria Masonia), daughter of the consul Gaius Papirius Maso (consul in 231 BC), whom he divorced, according to Plutarch, for no particular reason. From this marriage, four children were born: two sons and two daughters, the elder Aemilia Paulla Prima apparently married to the son of Marcus Porcius Cato, and the younger Aemilia Paulla Secunda to Aelius Tubero, a rich man of a plebeian family. He divorced his wife while his younger son was still a baby, according to Roman historians; thus the divorce probably took place around 183 BC-182 BC. Nevertheless, he was elected consul in 182 BC.
Paulus Macedonicus then married a second time (this wife's name is unknown) and had two more sons, the elder born around 181 BC and the younger born around 176 BC. He also apparently had another daughter (Aemilia Tertia), who was a small girl when her father was chosen consul for the second time.
Since four boys were too many for a father to support across the cursus honorum, Paulus decided to give the oldest two boys up for adoption, probably between 175 BC and 170 BC. The elder was taken by a Quintus Fabius Maximus and became Quintus Fabius Maximus Aemilianus, thus joining his fortunes to the house of a national hero. The younger, possibly named Lucius, was adopted by his own cousin Publius Cornelius Scipio, elder son and heir of Scipio Africanus, and became Publius Cornelius Scipio Aemilianus, thus falling heir to the legacy of Rome's most influential political dynasty.
With the eldest sons safely adopted by two of the most powerful patrician houses, Paulus 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 Paulus celebrated his Triumph. The elder of the two remaining sons was 14 and the younger 9, according to Polybius. Their names are unknown to us. The successes of his political and military career were thus not accompanied by a happy family life.
At his death, his sons Quintus Fabius Maximus Aemilianus and Publius Cornelius Scipio Africanus Aemilianus received his property by his will, even though they were legally no longer Aemilii Paulli; Scipio gave his share to his older brother who was less wealthy. Paulus's second wife (whose name is unknown to us) received her dowry back from the sale of some of her late husband's property. (Livy and Polybius both claim that Paulus died relatively poor, and that he had kept little for himself from the successful Macedonian campaign). His married daughters had presumably received dowries from their father; Aemilia Paulla Prima is known to have married in or around 164 BC.
With the death of Macedonicus, the Aemilii Paulii became extinct, even though he had two living sons. His elder surviving son Fabius Aemilianus eventually became consul and fathered at least one son, who in turn became consul as Fabius Allobrigicus in 121 BC. This man, in turn, may have been the ancestor of later Fabii who tied their fortunes to Julius Caesar and Augustus. The younger surviving son was more famous as Scipio Aemilianus but died leaving no known issue. Of the daughters, the elder was ancestor of at least two consuls of no particular distinction. The younger was mother of a consul Quintus Aelius Tubero.
His first and former wife Papiria Masonia survived her ex-husband and lived to enjoy her former sister-in-law's property presented to her by her younger son (per Polybius). At her death, her property was divided between her sons, but Scipio gave it to his sisters.