Macrinus was born in the Mauretania Roman province in an equestrian middle class family, as opposed to aristocratic senatorial class. As a young man, Macrinus studied enough to permit him ascension in the Roman hierarchy. Under emperor Lucius Septimius Severus he became an important bureaucrat and emperor Caracalla nominated him prefect of the Praetorian guard. The post was the highest a knight of the equestrian order could achieve in those times. The prefect was second in command to the emperor and responsible for the only military force present in the city of Rome. In the first years of his appointment, Macrinus had certainly the trust of Caracalla, however he began to plot against the emperor.
In 217, Caracalla headed East to prepare a campaign against the Parthian Empire. Macrinus was among his staff, as well as other members of the praetorian guard. In April, the emperor, known as a very religious man, went to visit a temple, near the spot of the battle of Carrhae, accompanied only by his bodyguard which included Macrinus. Events are not clear, but it is certain that Caracalla was murdered at some point of the trip and on the return in April 11, Macrinus proclaimed himself emperor. He was the first man to became so without being a previous member of the Senate. Macrinus also nominated his son Diadumenianus Caesar and successor.
The first months of reign were not successful. On the news of Caracalla's death, the Persian emperor invaded the Roman lands, conquered to him in the previous years. Moreover, Macrinus decided to remain in the East and discontent rose in Rome. The situation with the legions was not promising either, due to the imposed reforms in the paying system which favoured veterans over the recruits.
The royal family, headed by Julia Maesa and her daughters Julia Bassiana and Julia Mamaea, was evicted from the imperial palace and ordered to return home. For the Severan women, home was in Syria in the East where the emperor was. Since Macrinus was unable to consolidate his rule, they began to plot a revolt in favor of Bassiana's son Heliogabalus, now publicized as Caracalla's illegitimate son and heir. The rebellion started on May 15 and on June 8 of 218, Macrinus' troops were defeated in battle. Macrinus managed to escape and sent Diadumenianus as an ambassador to the Persian court. He was heading to Rome to secure the city for his cause but was caught in Asia Minor and executed for usurping the crown. Diadumenianus would suffer the same fate at the hands of the Persians.