The Celts were the first population in the territory of present-day Slovakia who can be identified on the basis of written sources. The first Celtic groups came from the West around 400 BC. Settlements of the La Tène culture indicate that the Celts colonized the lowlands along the river Danube and its tributaries. The local population was either subjected by the Celts or withdrew to the mountainous northern territory. New Celtic groups arrived from Northern Italy during the 2nd century BC. The Celts initially lived in tiny huts – 4 by 3 metres (13 ft × 10 ft) in size – which either formed small villages or were scattered across the countryside.
Some of the small hill forts which were built in the 1st century BC developed into important local economic and administrative centers. For example, the hill fort at Zemplín was a center of iron-working; glass works were unearthed at Liptovská Mara; and local coins were struck at Bratislava and Liptovská Mara. Coins from Bratislava bore inscriptions like Biatec and Nonnos. The fort at Liptovská Mara was also an important center of the cult of the bearers of the Púchov culture of the Northern Carpathians.
Burebista, King of the Dacians, invaded the Middle Danube region and subjugated the majority of the local Celtic tribes (the Boii and the Taurisci) around 60 BC. Burebista's empire collapsed after he died about 16 years later. Archaeological sites yielding painted ceramics and other artefacts of Dacian provenance suggest that Dacian groups settled among the local Celts in the region of the rivers Bodrog, Hron and Nitra. The spread of the "Púchov culture", associated with the Celtic Cotini, shows that the bearers of that culture started a northward expansion during the same period.
The Romans and the Germanic tribes launched their first invasions against the territories along the Middle Danube in the last decade of the 1st century BC. Roman legions crossed the Danube near Bratislava under the command of Tiberius to fight against the Germanic Quadi in 6 AD, but the local tribes' rebellion in Pannonia forced the Romans to return. Taking advantage of internal strifes, the Romans settled a group of Quadi in the lowlands along the Danube between the rivers Morava and Váh in 21, making Vannius their king. The Germans lived in rectangular houses, rather than square ones, and cremated their dead, placing the ashes in an urn.
Although the Danube formed the frontier between the Roman Empire and the "Barbaricum", the Romans built small outposts along the left bank of the Danube, for instance, at Iža and Devín. During the same period, the Germanic tribes were expanding to the north along the rivers Hron, Ipeľ and Nitra. Roman troops crossed the Danube several times during the Marcomannic Wars between 160 and 180. Emperor Marcus Aurelius accomplished the first chapter of his Meditations during a campaign against the Quadi in the region of the Hron River in 172.] The "Miracle of the Rain" – a storm which saved an exhausted Roman army – occurred in the land north of the Danube in 173; Christian authors attributed it to a Christian soldier's prayer. Roman troops crossed the Danube for the last time in 374, during Emperor Valentinian I's campaign against the Quadi who had allied with the Sarmatians and invaded the Roman province of Pannonia.