Kastel was first mentioned as a Mainz bridgehead around 10 BC. Under the threat of the Alamanni, the protection of the fort was improved in the first century by building walls around the settlement. Around 71, a stone bridge was built under Emperor Vespasian, which still existed during the reign of Emperor Maximian. It led into today's Große Kirchenstrasse / Rathausstrasse, directly into the Roman fort, whose second gate was located just a few meters away from the foundation of the Roman Arch of Honour, which was discovered in 1986. The civilian settlement, which was established in the 2nd century, was called "castellum matiacorum". The bridge, which was destroyed at the beginning of the 4th century, was rebuilt by Charlemagne in 803, using the Roman pile grating; however, it was destroyed by fire in 813. After that, the river could only be crossed using primitive ferries. It was not until the 17th century that a ship bridge was built again. In the 10th century, Kastel was an imperial estate. Later, large parts passed to the diocese of Mainz, whose land ownership in Kastel has been documented since the 11th century. The right of patronage over the churches was exercised by St. Peter's Abbey in Mainz, as evidenced by the names Petersberg and Petersaue. Other spiritual landowners were the Teutonic Knights, the Jakobsberg Monastery and the Mainz Hospital for the Poor of the Holy Spirit, which gave its name to the Spittelstück district.

The ecclesiastical history of Kastel dates back to late antiquity. According to legend, the soldier-martyr Ferrutius died in Kastel. A parish church is not documented until 1147, and a priest is named in 1281. A church dedicated to St. George probably dates back to the 6th century. Its patronage was later transferred to a chapel dedicated to the Assumption of the Virgin Mary within the town fortifications, documented in 1450. This new, younger St. George's Church was rebuilt after the destruction of Kastel in the 17th century and consecrated in 1746. It was completely destroyed during the bombing of Kastel in 1944; a completely modified new building was erected by 1977. There is evidence of a Brotherhood of St. James in Kastel since 1127.

Kastel was first mentioned as a town in 1237. From 1240, the town was involved in military conflicts between the Hohenstaufen dynasty and the nobility of the Middle Rhine and was destroyed and rebuilt several times. In 1484, the Archbishop of Mainz, Berthold von Henneberg, had Kastel secured by, among other things, a fortification with four towers, including the Erbenheimer Warte. From this time onwards, the Metropolitan of Mainz was the undisputed ruler of the town. One of the oldest markets in the region, Bartholomew's Market, was established in 1475. The population lived from agriculture and viticulture. The representative of the secular authorities was the Schultheiß (mayor), who can be traced back to the middle of the 14th century. The bailiff represented the ecclesiastical lord of the town. A court seal with the church patron St. George on the seal dates from 1453. The court and town hall of Kastel was first mentioned in a document in 1510. It was destroyed by the French in 1689, rebuilt in 1755 and replaced by a new building in the 1880s. A new ship bridge was built in 1661; in 1690 there were 1,100 inhabitants and 225 houses in Kastel. Warlike conflicts and the aftermath of the Thirty Years' War took their toll on the town in the 17th century. In 1666, more than half of the population was carried off by the plague. To contain the plague, a so-called plague wall was built around the church of St. George, behind which the sick were cared for and the deceased buried. Parts of it are still preserved today. In 1689, the French burned down the town. From 1792, the fortress of Kastel was used as a military bridgehead by the French revolutionary army under General Custine and later by Napoleon. In 1816, Austria and Prussia took over the fortifications and extended them in 1832/33 to include the Reduit defensive complex on the banks of the Rhine.

There had been a school in Kastel since the beginning of the 17th century. The teacher also held the office of court clerk, bell ringer and organist. Classes were probably initially held in the town hall before a separate schoolhouse was built in 1671. In 1841, it was replaced by a building in Eisenbahnstraße, which was suitable for four classes. In 1911, all classes were integrated into a new large school building on Ludwigsplatz, which was renamed Gustav Stresemann School after the incorporation in 1963. Around 1900, there were two Catholic and one Protestant elementary school. The Wilhelm Leuschner School was added in 1975. The majority of the population was Catholic. It was not until 1859 that a Protestant congregation was founded, which was given its own church in 1878. An independent Jewish community, whose beginnings date back to the 15th century, existed until the transfer to Mainz in 1914. At least five Jewish families are documented in 1452. Around 1700 there were again Jews living in Kastel, who formed a community together with those in Kostheim; in total there were around 12 to 14 Jewish families. In 1843, the community had grown to 97 people. In 1833/34, a synagogue with a community center was built in Frühlingsstraße, which was sold after the community was dissolved in 1914 and later demolished. From 1814, the community had its own teacher and precentor, and there had also been an infirmary since 1830. The dead were buried in Mainz. Even after 1914, there were still Jewish residents in Kastel, 24 of whom became victims of the Holocaust.

After the withdrawal of the French, Kastel continued to be co-administered by Mainz from May 1814, before both towns were assigned to the Grand Duchy of Hesse in Darmstadt as federal fortresses after the Congress of Vienna in 1815. It was not until 1908 that Kastel was finally incorporated into Mainz. Finally, in 1945, Kastel, together with Amöneburg and Kostheim, was incorporated into the urban district of Wiesbaden. In the 16th century, the great era of the raftsmen began. Christof Ruthof GmbH Schiffswerften und Maschinenfabrik was an important employer. The first Rhine steamers began operating in 1825. Kastel was connected to the Taunusbahn from Frankfurt am Main to Wiesbaden in 1839. The revolutionary movement of 1848 did not stop at Kastel; the mayor, policeman and schoolmaster were deposed. In 1882-85, today's Theodor Heuss Bridge was built. In 1896, drawbridges and gates were demolished in Kastel, and in 1904 the inner wall was also removed. Now the waterworks were built at the Ochsenbrunnen, Kastel was given a sewage system and connections to the gas and electricity networks. The Kastel clubs - the volunteer fire department from 1866, the rowing and canoeing society from 1880, the gymnastics and sports clubs from 1846/1886 and the Jocus-Garde from 1889 - have a long tradition. Kastel is a carnival stronghold, and the carnival club is one of the four organizers of the television session that is broadcast nationwide every year on the Friday before the carnival weekend.

The Second World War had devastating consequences for Kastel. The bombing by the British and American air force on 8 September 1944 led to the almost complete destruction of the town center. Over 300 inhabitants were killed. Modern Kastel has developed beyond the 21-hectare site of the Air Forces Europe Exchange in the north of the town center, which is still used for military purposes. The largest new development areas, "Krautgärten" and "An der Helling", have been built since the mid-1990s. In 2015, 12,537 people lived in Kastel in 5,972 households. Catholic Christians are strongly represented with over 50% of the population, while the Protestant community accounts for just under 40% of the population. Around 20% of the population are migrants.