S. williamsi has been grouped within a clade of seven other species that are believed to have diverged from their ancestors around 20 million years ago.

During the day, individuals can be found basking on thin branches relying on their camouflage colouration to protect them from predators.

Studies conducted by Eric Pianka depict that the tails of eastern spiny-tailed geckos have evolved to obtain antipredator functions and are also commonly used in behavioural displays.

[9] The caudal glands are able to project thin streams of a sticky, noxious and odorous substance through the skin ruptures of the mid-dorsal line of the tail.

This may also be due to the elaboration of tubercles surrounding the caudal glands as many other species of gecko rely solely on autotomy to escape predators.

There are numerous ecosystems and ecoregions which the eastern spiny-tailed gecko inhabits with different vegetation structure and composition.

In central NSW and south-west QLD, the semi-arid biome makes up the greatest area of occupation for the species with multiple shifts into surrounding sclerophyll and monsoon communities.

[2] Females lay two clutches of two eggs at a time which are generally laid at the base of trees, under rocks or in abandoned burrows that are no longer occupied by other animals.

Strophurus williamsi has been evaluated and categorised by the IUCN as a species of least concern meaning that they are not a focus for conservation because they are not threatened.

The species is however, vulnerable to pressure by grazing and habitat loss, mostly occurring due to land clearing for agriculture.

Predators of the eastern spiny-tailed gecko include feral cats, larger lizards such as goannas, birds of prey.