Alexius' mother wielded great influence during his reign, and he is described by his daughter, the historian Anna Comnena, as running next to the imperial chariot that she drove. In 1074, the rebel mercenaries in Asia Minor were successfully subdued, and, in 1078, he was appointed commander of the field army in the West by Nicephorus III. In this capacity, Alexius defeated the rebellions of two successive governors of Dyrrhachium, Nicephorus Bryennius (whose son or grandson later married Alexius' daughter Anna) and Nicephorus Basilakes. Alexios was ordered to march against his brother-in-law Nicephorus Melissenus in Asia Minor but refused to fight his kinsman. This did not, however, lead to a demotion, as Alexius was needed to counter the expected Norman invasion led by Robert Guiscard near Dyrrhachium.
While the Byzantine troops were assembling for the expedition, Alexius was approached by the Ducas faction at court, who convinced him to join a conspiracy against Nicephorus III. Alexius was duly proclaimed emperor by his troops and marched on Constantinople. Bribing the western mercenaries guarding the city, the rebels entered Constantinople in triumph, meeting little resistance on April 1, 1081. Nicephorus III was forced to abdicate and retire to a monastery, and Patriarch Cosmas I crowned Alexius I emperor on April 4.
During this time, Alexius was rumored to be the lover of Empress Maria of Alania, the daughter of King Bagrat IV of Georgia, who had been successively married to Michael VII Ducas and his successor Nicephorus III Botaneiates, and was renowned for her beauty. Alexius arranged for Maria to stay on the palace grounds. It was also thought that Alexius may have been considering marrying the erstwhile empress. However, his mother consolidated the Ducas family connection by arranging the Emperor's marriage to Irene Ducaena, granddaughter of the Caesar John Ducas, the uncle of Michael VII, who would not have supported Alexius otherwise. As a measure intended to keep the support of the Ducae, Alexius restored Constantine Ducas, the young son of Michael VII and Maria, as co-emperor and a little later betrothed him to his own first-born daughter Anna, who moved into the Mangana Palace with her fiancé and his mother.
However, this situation changed drastically when Alexius' first son John II Comnenus was born in 1087: Anna's engagement to Constantine was dissolved, and she was moved to the main Palace to live with her mother and grandmother. Alexius became estranged from Maria, who was stripped of her imperial title and retired to a monastery, and Constantine Ducas was deprived of his status as co-emperor. Nevertheless, he remained in good relations with the imperial family and succumbed to his weak constitution soon afterwards.
Alexius' long reign of nearly thirty-seven years was full of struggle. At the very outset, he had to meet the formidable attack of the Normans (led by Robert Guiscard and his son Bohemund), who took Dyrrhachium and Corfu, and laid siege to Larissa in Thessaly (see Battle of Dyrrhachium). Alexius suffered several defeats before being able to strike back with success. He enhanced this by bribing the German king Henry IV with 360,000 gold pieces to attack the Normans in Italy, which forced the Normans to concentrate on their defenses at home in 1083–1084. He also secured the alliance of Henry, Count of Monte Sant'Angelo, who controlled the Gargano Peninsula and dated his charters by Alexius' reign. Henry's allegiance was to be the last example of Byzantine political control on peninsular Italy. The Norman danger ended for the time being with Robert Guiscard's death in 1085, and the Byzantines recovered most of their losses.
Alexius had next to deal with disturbances in Thrace, where the heretical sects of the Bogomils and the Paulicians revolted and made common cause with the Pechenegs from beyond the Danube. Paulician soldiers in imperial service likewise deserted during Alexius' battles with the Normans. As soon as the Norman threat had passed, Alexius set out to punish the rebels and deserters, confiscating their lands. This led to a further revolt near Philippopolis, and the commander of the field army in the west, Gregory Pakourianos, was defeated and killed in the ensuing battle. In 1087 the Pechenegs raided into Thrace and Alexius crossed into Moesia to retaliate but failed to take Dorostolon (Silistra). During his retreat, the emperor was surrounded and worn down by the Pechenegs, who forced him to sign a truce and pay protection money. In 1090 the Pechenegs invaded Thrace again, while the brother-in-law of the Sultan of Rum launched a fleet and attempted to arrange a joing siege of Constantinople with the Pechenegs. Alexius overcame this crisis by entering into an alliance with a horde of 40,000 Cumans, with whose help he crushed the Pechenegs at Levounion in Thrace on April 29, 1091.
This put an end to the Pecheneg threat, but in 1094 the Cumans began to raid the imperial territories in the Balkans. Led by a pretender claiming to be Constantine Diogenes, a long-dead son of the Emperor Romanos IV, the Cumans crossed the mountains and raided into eastern Thrace until their leader was eliminated at Adrianople. With the Balkans more or less pacified, Alexius could now turn his attention to Asia Minor, which had been almost completely overrun by the Seljuk Turks.
As early as 1090, Alexius had taken reconciliatory measures towards the Papacy, with the intention of seeking western support against the Seljuks. In 1095 his ambassadors appeared before Pope Urban II at the Council of Piacenza. The help which he wanted from the West was simply mercenary forces and not the immense hosts which arrived, to his consternation and embarrassment, after the pope preached the First Crusade at the Council of Clermont later that same year. Not quite ready to supply this number of people as they traversed his territories, the emperor saw his Balkan possessions subjected to further pillage at the hands of his own allies. Alexius dealt with the first disorganized group of crusaders, led by the preacher Peter the Hermit, by sending them on to Asia Minor, where they were massacred by the Turks in 1096.
The second and much more formidable host of crusaders gradually made its way to Constantinople, led in sections by Godfrey of Bouillon, Bohemund of Taranto, Raymond IV of Toulouse and other important members of the western nobility. Alexius used the opportunity of meeting the crusader leaders separately as they arrived and extracting from them oaths of homage and the promise to turn over conquered lands to the Byzantine Empire. Transferring each contingent into Asia, Alexius promised to supply them with provisions in return for their oaths of homage. The crusade was a notable success for Byzantium, as Alexius now recovered for the Byzantine Empire a number of important cities and islands. The crusader siege of Nicaea forced the city to surrender to the emperor in 1097, and the subsequent crusader victory at Dorylaion allowed the Byzantine forces to recover much of western Asia Minor. Here Byzantine rule was reestablished in Chios, Rhodes, Smyrna, Ephesus, Sardis, and Philadelphia in 1097–1099. This success is ascribed by his daughter Anna to his policy and diplomacy, but by the Latin historians of the crusade to his treachery and falseness. In 1099, a Byzantine fleet of 10 ships were sent to assist the Crusaders in capturing Laodicea and other coastal towns as far as Tripoli. The crusaders believed their oaths were made invalid when the Byzantine contingent under Tatikios failed to help them during the siege of Antioch; Bohemund, who had set himself up as Prince of Antioch, briefly went to war with Alexius in the Balkans, but was blockaded by the Byzantine forces and agreed to become Alexius' vassal by the Treaty of Devol in 1108.
During the last twenty years of his life Alexius lost much of his popularity. The years were marked by persecution of the followers of the Paulician and Bogomil heresies—one of his last acts was to publicly burn on the stake Basil, a Bogomil leader, with whom he had engaged in a theological dispute. In spite of the success of the crusade, Alexius also had to repel numerous attempts on his territory by the Seljuks in 1110–1117.
Alexius was for many years under the strong influence of an eminence grise, his mother Anna Dalassena, a wise and immensely able politician whom, in a uniquely irregular fashion, he had crowned as Augusta instead of the rightful claimant to the title, his wife Irene Ducaena. Dalassena was the effective administrator of the Empire during Alexius' long absences in military campaigns: she was constantly at odds with her daughter-in-law and had assumed total responsibility for the upbringing and education of her granddaughter Anna Comnena.
Alexius' last years were also troubled by anxieties over the succession. Although he had crowned his son John II Comnenus co-emperor at the age of five in 1092, John's mother Irene Doukaina wished to alter the succession in favor of her daughter Anna and Anna's husband, Nicephorus Bryennius. Bryennios had been made kaisar (Caesar) and received the newly-created title of panhypersebastos ("honoured above all"), and remained loyal to both Alexius and John. Nevertheless, the intrigues of Irene and Anna disturbed even Alexius' dying hours.
Alexius I had stabilized the Byzantine Empire and overcome a dangerous crisis, inaugurating a century of imperial prosperity and success. He had also profoundly altered the nature of the Byzantine government. By seeking close alliances with powerful noble families, Alexius put an end to the tradition of imperial exclusivity and coopted most of the nobility into his extended family and, through it, his government. This measure, which was intended to diminish opposition, was paralleled by the introduction of new courtly dignities, like that of panhypersebastos given to Nicephorus Bryennius, or that of sebastokrator given to the emperor's brother Isaac Comnenus. Although this policy met with initial success, it gradually undermined the relative effectiveness of imperial bureaucracy by placing family connections over merit. Alexius' policy of integration of the nobility bore the fruit of continuity: every Byzantine emperor who reigned after Alexius I Comnenus was related to him by either descent or marriage.