When the civil war broke out in 49 between Caesar and Pompey, it was believed that Brutus would join the party of Caesar; but Brutus, who saw in Pompey the champion of the aristocracy, suppressed his personal feelings towards the murderer of his father, and followed the example of Cato, who declared for Pompey. Brutus, however, did not accompany Cato, but went with P. Sextius to Cilicia, probably to arrange matters with his debtors in Asia, and to make preparations for the war. In 48, he distinguished himself in the engagements in the neighbourhood of Dyrrhachium, and Pompey treated him with great distinction. In the battle of Pharsalia, Caesar gave orders not to kill Brutus, probably for the sake of Servilia, who implored Caesar to spare him. (Plut. Brut. 5.) After the battle, Brutus escaped to Larissa, but did not follow Pompey any further. Here he wrote a letter to Caesar soliciting his pardon, which was generously granted by the conqueror, who even invited Brutus to come to him. Brutus obeyed, and, if we may believe Plutarch (Plut. Brut. 6), he informed Caesar of Pompey's flight to Egypt. As Caesar did not require Brutus to fight against his former friends, he withdrew from the war, and spent his time either in Greece or at Rome in his favourite literary pursuits, He did not join Caesar again till the autumn of 47 at Nicaea in Bithynia, on which occasion he endeavoured to interfere with the conqueroron behalf of a friend of king Deiotarus, but Caesar refused to comply with the request. In the year following Brutus was made governor of Cisalpine Gaul, though he had been neither praetor nor consul; and he continued to serve the dictator Caesar, although the latter was making war against Brutus's own relatives in Africa. The provincials in Cisalpine Gaul were delighted with the mild treatment and justice of Brutus, whom they honoured with public monuments : Caesar too afterwards testified his satisfaction with his administration. As his province was far from the scene of war, Brutus as usual devoted his time to study. At this time, Cicero made him one of the speakers in the treatise which bears the name of Brutus, and in 46 he dedicated to him his Orator. In 45, Brutus was succeeded in his province by C. Vibius Pansa, but did not go to Rome immediately. Before his return, he published his eulogy on Cato, in which Cicero found sentiments that hurt his vanity, as his suppression of the conspiracy of Catiline was not spoken of in the terms he would have liked. Accordingly, upon the arrival of Brutus at one of his country-seats near Rome, a certain degree of coldness and want of confidence existed between the two, although they wrote letters to each other, and Cicero, on the advice of Atticus, even dedicated to him his work About this time, Brutus divorced Claudia, apparently for no other reason than that he wished to marry Portia, the daughter of Cato. After the close of Caesar's war in Spain, Brutus went from Rome to meet him, and, in the beginning of August, returned to the city with him.

In 44 Brutus was praetor urbanus, and C. Cassius, who had been disappointed in his hope of obtaining the praetorship, was as much enraged against Brutus as against the dictator. Caesar promised Brutus the province of Macedonia, and also held out to him hopes of the consulship. Up to this time Brutus had borne Caesar's dictatorship without expressing the least displeasure; he had served the dictator and paid homage to him, nor had he thought it contrary to his republican principles to accept favours and offices from him. His change of mind which took place at this time was not the result of his reflections or principles, but of the influence which Cassius exercised over him. He was persuaded by Cassius to join the conspirators who murdered Caesar on the 15th of March, 44. After the deed was perpetrated he went to the forum to address the people, but found no favour. The senate, indeed, pardoned the murderers, but this was only a farce played by M. Antony to obtain their sanction of the Julian laws. The murderers then assembled the people on the capitol, and Brutus in his speech promised that they should receive all that Caesar had destined for them. All parties were apparently reconciled. But the arrangements which Antony made for the funeral of Caesar, and in consequence of which the people made an assault upon the houses of the conspirators, shewed them clearly the intentions of Antony. Brutus withdrew into the country, and during his stay there he gave, in the month of July, most splendid Ludi Apollinares, hoping thereby to turn the disposition of the people in his favour. But in this he was disappointed, and as Antony assumed a threatening position, he sailed in September to Athens with the intention of taking possession of the province of Macedonia, which Caesar had assigned him, and of repelling force by force. After staying at Athens a short time in the company of philosophers and several young Romans who attached themselves to his cause, and after receiving a very large sum of money from the quaestor M. Appuleius, who brought it from Asia, Brutus intended to proceed to Macedonia. But the senate had now assigned this province to Antony, who, however, towards the end of the year, transferred it to his brother, the praetor C. Antonius. Before, however, the latter arrived, Brutus, who had been joined by the scattered troops of Pompey, marched into Macedonia, where he was received by Q. Hortensius, the son of the orator, as his legitimate successor. Brutus found an abundance of arms, and the troops stationed in Illyricum, as well as several other legions, joined him. C. Antonius, who also arrived in the meantime, was unable to advance beyond the coast of Illyricum, and at the beginning of 43 was besieged in Apollonia and compelled to surrender. Brutus disregarded all the decrees of the senate, and resolved to act for himself. While Octavianus in the month of August 43 obtained the condemnation of Caesar's murderers, Brutus was engaged in a war against some Thracian tribes to procure money for himself and booty for his soldiers. About this time he assumed the title imperator, which, together with his portrait, appear on many of his coins. The things which were going on meantime in Italy seemed to affect neither Brutus nor Cassius, but after the triumvirate was established, Brutus began to prepare for war. Instead, however, of endeavouring to prevent the enemy from landing on the coast of the Ionian sea, Brutus and Cassius separated their forces and ravaged Rhodes and Lycia. Loaded with booty, Brutus and Cassius met again at Sardis in the beginning of 42, but it was only the fear of the triumvirs that prevented them from falling out with each other. Their carelessness was indeed so great, that only a small fleet was sent to the Ionian sea under the command of Statius Murcus. Before leaving Asia, Brutus had a dream which foreboded his ruin at Philippi, and in the autumn of 42 the battle of Philippi was fought. In the first engagement Brutus conquered the army of Octavianus, while Cassius was defeated by Antony. But in a second battle, about twenty days later, Brutus was defeated and fell upon his own sword.

From his first visit to Asia, Brutus appears as a man of considerable wealth, and he afterwards increased it by lending money upon interest. He possessed an extraordinary memory and a still more extraordinary imagination, which led him into superstitions differing only from those of the multitude by a strange admixture of philosophy. He was deficient in knowledge of mankind and the world, whence he was never able to foresee the course of things, and was ever surprised at the results. Hence also his want of independent judgment. The quantity of his varied knowledge, which he had acquired by extensive reading and his intercourse with philosophers, was beyond his control, and was rather an encumberance to him than anything else. Nothing had such charms for him as study, which he prosecuted by day and night, at home and abroad.