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Due to the proximity of Danube, Isaccea represents a real hearth of history.

Archaeological investigations revealed the existence of a Neolithic settlement 7000 years old at the north-western extremity of the locality.

Noviodunum citadel, which ruins are at 2 km east from the actual town, elevated on a promontory over 20 m high, at the point "Pontonul vechi" or "Eski-Kale" (in Turkish "The old Fortress"), has a special importance.

Located near one of the most important ford of the Danube, on an over 20 m high promontory, the fortress had, in different historical periods, a special military and commercial role.
Built as early as the first period of the Principality epoch, above an old Gaetic settlement, its name having a Celtic etymology, the fortress was, first of all, a base of the Low Danube Roman fleet Classis Flavia Moesica, then headquarters of some Legio V Macedonica and Legio I Italica detachments. It represented also an important crossing point. Here the military and commercial route coming from Marcianopolis through the center of Dobrudja crossed the Danubian limes. The early Roman fortress (I - III A.D.) was raised at the municipium position at the time of Severs. Many important buildings, situated on the Danube bank, are still visible: thermae, dwellings, fragments of the precinct wall, a tumular necropolis from I - III A.D. It was an urbane cosmopolitan center, its population consisting of soldiers, veterans and Romans or oriental Greeks civilians. The proper fortress was doubled by an ample civilian settlement surrounded by a defensive system consisting in three earth walls with groove. On the south-eastern platform the fortress necropolis pointed by numerous funeral hillocks, between them the huge hillock kurgan-vizier standing out, was placed.

The fortress was destroyed by the attacks of the Goths and Heruli around the year 267. It was rebuilt, at smaller sizes, at the time of the emperors Aurelian and Probus. From this period, there were unearthed: the northern precinct with 7 semi-circular defense towers, the access gate to the harbor installation, thermae, a basilica, a big tower which surface is about 225 m² on the southern side of the fortress. The late fortress (IV - VII A.D.) stays all the period as headquarters of the Danube fleet, which name is now Classis Ripae Scythicae, and beginning with IV century headquarters for Legio I Iovia Scythica. The Christian hagiographic localize sources at Noviodunum a big number of martyrs (32 or 36), fact which shows the presence here of a strong Christian community. From this period a burial monument in a cross shape belonging to an IV century A.D. family was studied.

For two centuries (the beginning of VII A.D. to the third quarter of X A.D.) the urbane life has declined. In the end of X A.D. and the beginning of XI A.D., the fortress took back its defensive function, the precinct being rebuilt by the Byzantines on the old Roman-Byzantine foundations. In the next period it was conquered by the Tartars and afterwards ruled by Mircea the Old. The Turks conquered it in 1420. At that time, the fortress walls have been destroyed. In the XVI A.D., up on the fortress, the Turks built a trapezoidal camp surrounded by a precinct earthwork wall which protected a garrison.

Simultaneously, as early as XIII A.D., the core of the settlement has moved to the south, where a settlement named Isakdji (the name of the nowadays town Isaccea derives from it) had been founded, probably by the Tartars.

In 1331, the Arabian geographer Abulfeda mentions Isaccea as "a town in Wallachian's country", under the name Isakdji.

In 1417, the Ottoman Sultan Mehmed I undertakes a big expedition against Wallachia, the main fight taking place on Dobrudja's territory. Despite the firm resistance of the Mircea the Old soldiers, especially those who defended the fortresses Enisala and Isaccea, the province situated between Danube and Black Sea has been lost for four centuries.

During the Turkish domination, Isaccea was an important administrative, military and economic center.

In 1484, the chronicle of the Turkish historian Seadedin mentions Isaac when he tells about the expedition of Baiazid II.

At the time of the campaign against Poland, in 1621, the army of the sultan Osman I was stationed at Isaccea 8 days in order to build a bridge across the Danube. Still here, he will order the elevation of a castle.

Isaccea - or Obluciţa following some documents, was a ford for crossing the Danube very used by the Ottoman armies in the Middle Age, in the fight against Romanian Countries and Poland.

In 1677, during the Turkish - Polish war, following the information from the diary of the Kulm's Palatine, Isaccea was an open town situated on a hillock, without walls or defence works. The streets were very narrow, but with many houses. The locality had two mosques and many, but poor, shops. A palace, inhabited by the Sultan, was present here, too. On the Danube's bank, the castle (fortress) with four towers and very high walls was built.

In 1769, the great vizier Mahomed Emin Pasha, in time of the Russian-Turkish war from 1768 - 1774, settled his camp on the plain from Isaccea. At 15 October 1771, after the defeat of the Turkish, the fortress, the town and the mosques were burned, following the information given by Atanasie Comnen Ipsilante.

The Austrian map from 1790 notes the locality as Isakschi.

Following the information of Moltke from Campagnes des Russes dans la Turquie d' Europe, in April 1808, Isaccea had a garrison of 1500 people under command of Kursanli-Ali-Pasha. In August 1809, Isaccea had in the centre an old castle made in stone, probable for defense, and surrounded by a good retrenchment. The town had a charming position, it was elevated in the shape of an amphitheatre and it was surrounded by forests, gardens and vineyards.

In XIX century Isaccea was one one the 9 departments of Tulcea sanjak.

The military map from 1828 mentions the locality with the name Isaktia and at the middle of the XX century, Ion Ionescu de la Brad notes it with the name Sakicha or Sacce. He founds here 363 Romanians, 183 Turks, 163 Cossacks, 29 Greeks, 20 Jews and 3 Armenians, totally 784 inhabitants.

At the beginning of XX century, M.D. Ionescu wrote about Isaccea that "it was an old and badly kept up, with narrow streets. The main products of the region were: wood, wheat, but especially wine".

In 1900, in Isaccea were 618 houses, 1 inn, 11 shops, 10 mills and 21 fountains. The education was made in two schools, one for the boys and the other for the girls, both founded in 1882. A Turkish school, near the mosque, built in the XVIII century and two churches - "Sfântul Gheorghe" and "Sfinţii Voievozi", existed also in the town.

After 1928, Isaccea becomes town subordinated to the County's residence, Tulcea.

Those who put up in Isaccea can visit the ruins of the fortress Noviodunum, the grave of Isac-baba, considered by the Moslem population as the founder of the locality and used for Mohammedans rites, the mosque which is more than 300 years old and the church "Sfântul Gheorghe" - elevated at the end of XVIII century or at the beginning of XIX century, which possesses a high value wooden iconostasis dated in the period of Vasile Lupu (around 1645). The altar table has as base a burial monument from the Roman period.