The Serpentine, also called the snakes, are an ancient race of reptilian humanoids who were once the dominant species of Ninjago in the times of the First Spinjitzu Master. They warred with each other for countless years until banding together during the First Serpentine War to fight against the humans. Led by the sons of the First Spinjitzu Master and the Elemental Masters, the people of Ninjago rose up and locked them away in five separate tombs, one for each tribe (Anacondrai, Hypnobrai, Fangpyre, Constrictai, and Venomari). 40 years after the war, they were released by Lloyd Garmadon and Pythor, the latter of whom united the five tribes in a bid to conquer and destroy Ninjago. After claiming the Fangblades, Pythor unleashed the fabled Great Devourer from the Lost City of Ouroboros. The colossal serpent consumed Pythor and Master Wu and wreaked havoc on Ninjago City before being killed by Lord Garmadon.

After the death of the Devourer, the Serpentine were trapped in the tomb of the Stone Army. When the ninja were searching for the hard drive containing the Digital Overlord, they found the Serpentine, and Acidicus told them of the legend of the Golden Master. Shortly after, a group of Nindroids attacked the Serpentine, but the ninja defended them and defeated their adversaries. Though Skales declined to aid the ninja in their quest any further, when the Golden Master attacked Ninjago City, the Serpentine helped its citizens to flee below ground and escape the ensuing destruction. Pythor, who had been aiding the Golden Master, was turned minuscule after swallowing a shrinking pill.

With the Golden Master destroyed, the Serpentine resumed their lives in Ninjago, having redeemed themselves after protecting the city's people. When the ninja were rallying people to fight against Chen and his army of fake Anacondrai, the Serpentine joined the battle at the Corridor of Elders. Despite the new alliance, the fake Anacondrai made by Chen and Clouse were too powerful—leading Garmadon to sacrifice himself and be banished in order to free the spirits of the original Anacondrai to curse Chen's army. Following the battle, the Serpentine continued to live their normal lives while no longer having problems with humans for their help.

Sometime later, Krux used Great Devourer to breed a Vermillion Army to conquer Ninjago. They were finally defeated after being lost in the Temporal vortex.

Following a lengthy period of laze months after the Oni Invasion, the out of shape ninja embarked on a quest to help Professor Clutch Powers explore an Ancient Pyramid, with the purpose of honing their fading ninja skills. In the process, they accidentally freed vengeful Serpentine sorceress Aspheera from her magical entombment, leading her to steal Kai's Fire power and raise an army of mummified, fire-wielding Serpentine in an attempt to claim the Scroll of Forbidden Spinjitzu and exact her revenge on the "treacherous deceiver" who defeated her with the very same scroll. This culminated in a standoff in the Hangar Bay beneath the Monastery of Spinjitzu where Zane managed to defeat Aspheera and her army with the second scroll the ninja had stolen from the Explorers Club, though Aspheera managed to momentarily break free, unintentionally banishing the power-corrupt Nindroid to the Never-Realm, only to be imprisoned in Kryptarium Prison afterward.