In Roman times it was situated on the northern slopes of the hills Coressus and Pion and south of the Cayster (Küçükmenderes) River, the silt from which has since formed a fertile plain but has caused the coastline to move ever farther west. The Temple of Artemis, or Diana, to which Ephesus owed much of its fame and which seems to mark the site of the classical Greek (ancient Greek civilization) city, was probably on the seaboard when it was founded (about 600 BC), one mile east by northeast of Pion (modern Panayir Daǧ). In Roman times a sea channel was maintained with difficulty to a harbour well west of Pion. By late Byzantine times this channel had become useless, and the coast by the mid-20th century was three miles farther west. Ephesus commanded the west end of one great trade route into Asia, that along the Cayster valley, and had easy access to the other two, along the Hermus (Gediz) and the Maeander (Büyükmenderes) rivers.

Ephesus enters history in the mid-7th century BC, when it was attacked by the Cimmerians (Cimmerian). Unlike its neighbour, Magnesia, it survived the attacks. For part of the early 6th century the city was under tyrants. Though allied by marriage to the kings of Lydia, its people could not hold back the Lydian Croesus, who asserted a general suzerainty over the city. He did, however, present many columns and some golden cows for a new and splendid rebuilding of the Artemiseum (Temple of Artemis (Artemis, Temple of)). At this time, according to Strabo, the Ephesians began to live in the plain; and to this period, too, should be allotted the redrafting of the laws, said to have been the work of an Athenian, Aristarchus. Ephesus soon submitted to Cyrus (Cyrus II) of Persia (Greco-Persian Wars). Early in the Ionian revolt (499–493 BC) against the Persians, Ephesus served as a base for an Ionian attack on Sardis; but it is not mentioned again until 494, when the Ephesians massacred the Chiot survivors of the Battle of Lade. The massacre may have occurred because Ephesus was a commercial rival of the chief rebels, Chios and Miletus. Ephesus maintained friendly relations with Persia for about 50 years: in 478 Xerxes (Xerxes I), returning from his failure in Greece, honoured Artemis of Ephesus, although he sacked other Ionian shrines, and left his children for safety in Ephesus; and Themistocles landed there in the 460s on his flight to Persia. But after 454 Ephesus appears as a regular tributary of Athens. Great Ephesians up to this time had been Callinus, the earliest Greek elegist (mid-7th century BC), the satirist Hipponax, and the famous philosopher Heracleitus, one of the Basilids.

Ephesus shared in a general revolt of 412 BC against Athens, siding with Sparta in the Second Peloponnesian War, and remained an effective ally of Sparta down to the end of the war. Threatened by Persia after 403, Ephesus served in 396 as the headquarters of King Agesilaus (Agesilaus II) of Sparta. In 394 the Ephesians deserted to Conon's anti-Spartan maritime league, but by 387 the city was again in Spartan hands and was handed by Antalcidas to Persia. There followed the pro-Persian tyranny of Syrphax and his family, who were stoned to death in 333 on Alexander the Great's taking the city. After 50 years of fluctuating fortune, Ephesus was conquered by the Macedonian general Lysimachus and resettled around Coressus and Pion (286–281 BC). Lysimachus introduced colonists from Lebedus and Colophon and renamed the city after his wife, Arsinoo—a name soon dropped. This was the beginning of Ephesus' Hellenistic (Hellenistic Age) prosperity. It became conspicuous for the abundance of its coinage.

After the defeat of Antiochus the Great, king of Syria, by the Romans (ancient Rome) in 189 BC, Ephesus was handed over by the conquerors to the king of Pergamum. Attalus III (Attalus III Philometor Euergetes) of Pergamum bequeathed Ephesus with the rest of his possessions to the Roman people (133 BC). Thenceforth, Ephesus remained subject to Rome, except for a brief time beginning in 88 BC, when, at the instigation of Mithradates the Great (Mithradates VI Eupator) of Pontus, the cities of Asia Minor revolted and killed their Roman residents. The Ephesians even killed those Romans who had fled for refuge to the Artemiseum; notwithstanding which they returned in 86 BC to their former masters. Their claim, preserved on an extant inscription, that in admitting Mithradates they had merely yielded to superior force was rudely brushed aside by Sulla, who inflicted a very heavy fine. Although it twice chose the losing side in the Roman civil wars and although it was stoutly opposed by Pergamum and Smyrna, Ephesus became under Augustus the first city of the Roman province of Asia. The geographer Strabo wrote of its importance as a commercial centre in the 1st century BC. The triumphal arch of 3 BC and the aqueduct of AD 4–14 initiated that long series of public buildings, ornamental and useful, that make Ephesus the most impressive example in Greek lands of a city of imperial times.

Meanwhile the Christian (Christianity) Church began to win converts. A famous protest in the theatre against the teachings of St. Paul, described in Acts 19, is dated about AD 57. According to local belief Ephesus was the last home of the Virgin, who was lodged near the city by St. John and died there. The tradition that St. Luke also died there seems to be less strongly supported. Ephesus was one of the seven churches of Asia to which the Revelation to John was addressed.

The Goths (Goth) destroyed both city and temple in AD 262, and neither ever recovered its former splendour. The emperor Constantine, however, erected a new public bath, and Arcadius rebuilt at a higher level the street from the theatre to the harbour, named after him, the Arkadiane. A general council of the church, held at Ephesus in 431 in the great double church of St. Mary, condemned Nestorius and justified the cult of the Virgin as Theotokos (Mother of God). A few years later, according to legend, the Seven Sleepers of Ephesus (a group of 3rd-century Christian martyrs) were miraculously raised from the dead. They too became the object of a famous cult. The emperor Justinian (Justinian I) built the magnificent basilica of St. John in the 6th century. By the early Middle Ages, the city was no longer useful as a port and fell into decline; late Byzantine (Byzantine Empire) Ephesus, conquered by the Seljuqs in 1090, was merely a small town. After brief splendour in the 14th century, even this was deserted, and the true site of the Artemiseum remained unsuspected until 1869.

J.T. Wood, working at Ephesus for the British Museum between 1863 and 1874, excavated the odeum and theatre. In May 1869 he struck a corner of the Artemiseum. His excavation exposed to view not only the scanty remains of the latest edifice (built after 350 BC) but the platform below it of an earlier temple of identical size and plan subsequently found to be that of the 6th century BC, to which Croesus contributed. The sculptured fragments of both temples were sent to the British Museum. In 1904 D.G. Hogarth (Hogarth, David George), heading another mission from the museum, examined the earlier platform and found beneath its centre the remains of three yet older structures. In its earliest known phase the temple was apparently a small platform of green schist, containing a sealed deposit of primitive coins and other objects. These date from c. 600 BC.

It is impossible to assign the various architects named by ancient authors to the respective phases of the temple. At best, Chersiphron and Metagenes can be tentatively assigned to the Temple of Croesus, Chirocrates or Dinocrates to that of the 4th century. There had perhaps been some repairs toward 400 BC, associated with the architects Paeonius and Demetrius and with the prize-winning dedicatory hymn of the famous musician Timotheus. The Artemiseum passed rapidly through three phases before c. 550 BC. The Temple of Croesus (the fourth phase) was remarkable for its great size (it was more than 300 feet long and 150 feet wide), for the carved figures around the lower drums of its columns (columnae caelatae), and for the smaller but elaborate figured friezes along its roof gutter (sima). Croesus' temple seems to have been burned down in 356 BC. The new temple built shortly afterward copied the old in its columnae caelatae, one of which was by Scopas; but the new sima, instead of small, crowded figures, had a more conventional, if vigorous, rinceau ornament. The cella contained, among other great works, the Amazons of Polyclitus, Phidias, and Cresilas.

Lysimachean Ephesus has been continuously excavated since 1894 by the Austrian Archaeological Institute, but so solid and extensive is the Roman town that by the early 1960s the Austrians had rarely penetrated to Hellenistic levels.

On the hill of Ayasoluk (Hagios Theologos) is Justinian's church of St. John the Theologian, built around a shrine variously associated in the early Middle Ages with the death or bodily assumption of St. John. The church, uncovered since 1922, is a noble structure but badly restored. On the hill there is also a beautiful Seljuq mosque dedicated in 1375.

The public buildings of the city are arranged in a rectangular street pattern going back to Hellenistic days. They include the theatre, capable of seating nearly 25,000 spectators and completed in its present form under Trajan; the agora (marketplace), surrounded by stoas (sheltered promenades), dating from the time of Severus; the library of Celsus, also Trajanic and well known because of its facade; and an immense array of baths and gymnasiums.

All these buildings are to the west of Pion. On its north side is the stadium and north of this the gymnasium of Publius Vedius Antoninus, relatively small but very complete and with a notable chapel for the cult of Antoninus Pius. South of Pion were the odeum—another gift of Vedius—a roofed semicircular theatre to hold 1,400 persons; also a series of fountains and aqueducts, notably the aqueduct of Gaius Sextilius Pollio, which crossed the valley from Coressus. The unmortared city wall along the crest of Coressus appears to be that of Lysimachus.

Of the early Byzantine city, besides the stretch of curtain wall on Panajir Dağ, there remain the ruined church of the Seven Sleepers to its east and the long double basilica of the Virgin, the scene of the council, to its west. This basilica was rebuilt several times; it was largely around this building, between the great gymnasiums and the stadium of the classical city, that the early Byzantine Ephesians gathered.