Seleucus was the son of Antiochus from Orestis, one of Philip's generals, and of Laodice. In 333 BC, as a young man of about twenty-three, he accompanied Alexander into Asia and won distinction in the Indian campaign of 326 BC. In 324 BCE Seleucus took as wife Apama, with whom he had four children: two daughters, Apama and Laodice, and two sons, Antiochus & Achaeus.
When the Macedonian empire was divided in 323 BC (the "Partition of Babylon"), Seleucus was given the office of chiliarch, which attached him closely to the regent Perdiccas. Subsequently, Seleucus had a hand in the murder of Perdiccas during the latter's unsuccessful invasion of Egypt in 321 BC.
At the second partition, at Triparadisus (321 BC), Seleucus was given the government of the Babylonian satrapy. In 316 BC, when Antigonus had made himself master of the eastern provinces, Seleucus felt himself threatened and fled to Egypt. In the war which followed between Antigonus and the other Macedonian chiefs, Seleucus actively cooperated with Ptolemy and commanded Egyptian squadrons in the Aegean Sea.
The victory won by Ptolemy at the battle of Gaza in 312 BC opened the way for Seleucus to return to the east. His return to Babylon was afterwards officially regarded as the beginning of the Seleucid Empire and that year as the first of the Seleucid era. Master of Babylonia, Seleucus at once proceeded to wrest the neighbouring provinces of Persia, Susiana and Media from the nominees of Antigonus. Raids into Babylonia conducted in 311 BC by Demetrius, son of Antigonus, and by Antigonus himself in 311/310 (the Babylonian War), did not seriously check Seleucus' progress. Over the course of nine years (311-302 BC), while Antigonus was occupied in the west, Seleucus brought the whole eastern part of Alexander's empire as far as the Jaxartes and Indus Rivers under his authority.
In 305 BC, after the extinction of the old royal line of Macedonia, Seleucus, like the other four principal Macedonian chiefs, assumed the title and style of basileus (king). He established Seleucia on the Tigris as his capital.
As most historians note, Seleucus appears to have fared poorly as he did not achieve his aims. The two leaders ultimately reached an agreement, and through a treaty sealed in 305 BC, Seleucus ceded a considerable amount of territory to Chandragupta in exchange for 500 war elephants, which were to play a key role in the battles that were to come. According to Strabo, these were territories bordering the Indus:
Modern scholarship often considers that Seleucus actually gave more territory, in what is now southern Afghanistan, and parts of Persia west of the Indus. This would tend to be corraborated archaeologically, as concrete indications of Mauryan influence, such as the inscriptions of the Edicts of Ashoka, are known as far as Kandhahar, in today's southern Afghanistan.
Some authors claim this is an exaggeration, which comes from a statement made by Pliny the Elder, referring not specifically to the lands received by Chandragupta, but rather to the various opinions of geographers regarding the definition of the word "India" :
Also the passage of Arrian explaining that Megasthenes lived in Arachosia with the satrap Sibyrtius, from where he visited India to visit Chandragupta, goes against the notion that Arachosia was under Maurya rule:
Nevertheless, it is usually considered today that Arachosia and the other three regions did become dominions of the Mauryan Empire.
To cement the treaty, there was either some sort of marriage alliance (Epigamia) involving Seleucus' daughter or the diplomatic recognition of intermarriage between Indians and Greeks.
In addition to this matrimonial recognition or alliance, Seleucus dispatched an ambassador, Megasthenes, to the Mauryan court at Pataliputra (Modern Patna in Bihar state). The two rulers seem to have been on very good terms, as Classical sources have recorded that following their treaty, Chandragupta sent various presents such as aphrodisiacs to Seleucus.
Seleucus obtained knowledge of most of northern India, as explained by Pliny the Elder through his numerous embassies to the Mauryan Empire:
Seleucus apparently minted coins during his stay in India, as several coins in his name are in the Indian standard and have been excavated in India. These coins describe him as "Basileus" ("King"), which implies a date later than 306 BCE. Some of them also mention Seleucus in association with his son Antiochus as king, which would also imply a date as late as 293 BCE. No Seleucid coins were struck in India thereafter and confirm the reversal of territory west of the Indus to Chandragupta.
In 300 BCE, after the death of Apama, Seleucus married Stratonice, daughter of Demetrius Poliorcetes. Seleucus had a daughter by Stratonice, who was called Phila. In in 294 BC Stratonice married her stepson Antiochus. Seleucus reportedly instigated the marriage after discovering that his son was in danger of dying of lovesickness.
The possession of Syria gave him an opening to the Mediterranean, and he immediately founded the new city of Antioch on the Orontes as his chief seat of government. Seleucia on the Tigris continued to be the capital for the eastern satrapies. About 293 BC, he installed his son Antiochus there as viceroy, the vast extent of the empire seeming to require a double government.
It is said of Seleucus that "few princes have ever lived with so great a passion for the building of cities. He is reputed to have built in all nine Seleucias, sixteen Antiochs, and six Laodiceas".
The capture of Demetrius in 285 BC added to Seleucus's prestige. The unpopularity of Lysimachus after the murder of Agathocles gave Seleucus an opportunity for removing his last rival. His intervention in the west was solicited by Ptolemy Keraunos, who, on the accession to the Egyptian throne of his brother Ptolemy II (285 BC), had at first taken refuge with Lysimachus and then with Seleucus. War between Seleucus and Lysimachus broke out, and at the decisive battle of Corupedium in Lydia, Lysimachus fell (281 BC). Seleucus now held the whole of Alexander's conquests excepting Egypt in his hands, and moved to take possession of Macedonia and Thrace. He intended to leave Asia to Antiochus and content himself for the remainder of his days with the Macedonian kingdom in its old limits. He had, however, hardly crossed into the Chersonese when he was assassinated by Ptolemy Keraunos near Lysimachia (281 BC).