Stafford, along with neighbouring Everton Park and Stafford Heights, was originally known as Happy Valley. From around 1857 the area was mainly rural and industrial land: tanneries, fellmongeries, a quarry, brickworks and dairy farms, and it also served as the agistment paddocks for the Newmarket saleyards. The Stafford name arrived in 1886, when a new post office and school on Collier Street adopted it after a government administrator questioned whether "Happy Valley" was dignified enough for a new school, making Stafford one of the few places in Queensland to take its name directly from its school.

Growth stayed slow through the interwar years, with Stafford remaining largely semi-rural, until a Housing Commission estate went up during World War Two. Further development followed after the war, including a new brick school building on Stafford Road in 1948-49 and a shopping centre near the old tram terminus. That history has left Stafford with a genuinely large stock of 1940s-50s Housing Commission homes on quarter-acre blocks, standing alongside older Queenslander-style houses that predate the wartime estate. Properties on the suburb's original industrial land (former tannery, quarry or brickworks sites) can also have reworked ground that behaves differently to undisturbed residential soil.

For homeowners, that means Stafford's termite risk is shaped heavily by just how old most of the suburb's housing actually is: a wartime Housing Commission home is now well over 70 years old, and whatever termite protection it had at construction has long since reached the end of its useful life.