For humans, this is a painful sting, which leaves a sensation similar to what one feels when they get burned by fire — hence the name fire ant — and the aftereffects of the sting can be deadly to sensitive individuals. The venom is both insecticidal and antibiotic. Researchers have proposed that nurse workers will spray their brood to protect them from microorganisms. The worker ants are blackish to reddish and vary from 3–6 mm in length.

Their nests can appear as dome-shaped mounds, up to 40cm high, or can be found next to, or underneath other objects found on the ground, such as timber, logs, rocks, pavers, bricks etc. Mounds will not always be evident, but are usually found in open areas such as lawns, pastures, along roadsides and unused cropland. Mounds are rarely found in frequently cultivated areas. This species could easily be confused with the common coastal brown ant and as well as some local native ants.

Fire ants inflict a fiery sting, which causes a small blister or pustule to form at the site of each sting after several hours. The blisters become itchy while healing and are prone to infection if broken.  The venom of a fire ant sting causes stinging and swells into a bump. They can be very irritating at times, especially when stung repeatedly by several at once. The bump often forms into a white pustule, which is at risk of becoming infected.

The pustules are unattractive and uncomfortable while active and, if the bite sites become infected, can turn into scars. Some people are sensitive to the venom and experience anaphylaxis, which requires emergency treatment. Signs of anaphylaxis can include dizziness, nausea, sweating, low blood pressure, headache, and shortness of breath. If the fire ants can be brushed off before they inject their venom, pustules will not form. For all victims, immediately applying a solution of half bleach and half water can reduce pain, itching, and pustule formation. An antihistamine or topical corticosteroids may help reduce the itching. Rubbing aloe vera juice also reduces itching if applied immediately.

Most fire ant species don't bother people, and rarely come into contact with humans; of the few that do, most do not get the rank of serious pests, as they are kept in check by parasites, predators, and competition with other ants. However, at least one species, Solenopsis invicta, commonly known as the Red imported fire ant (RIFA), has been moved around the world from its native range in South America and, in the absence of its predators and parasites, has become a major pest nearly everywhere it has been introduced, as is common for invasive species. This species was accidentally introduced into the United States via Brazilian cargo entering the port of Mobile, Alabama, in the 1930s. The ants have since spread from coastal areas of Alabama and now infest large parts of the Southern U.S., and have created a nuisance to farmers and homeowners alike from California to Maryland. Ground nesting birds such as Bobwhite Quail have suffered decline due to fire ant intrusions. Since 2001, this species has been spread to eastern Australia, the Philippines, Taiwan, and China.

In the southern United States phorid flies have been imported as an attempt to control fire ants by natural means. The genus Apocephalus, or ant-decapitating fly, of which 110 species have been documented, is a parasite of the ant in South America. Members of Apocephalus reproduce by laying eggs in the head of the ant. The larvae eat the contents of the fire ant's head and emerge several days later. The phorid flies have been widely introduced throughout the U. S. Southeast, starting with Travis, Brazos, and Dallas counties in Texas, as well as Mobile, Alabama, where the ants first entered North America. Not all introductions have been successful, but the fly has been established in some sites in every southeastern state. Also the parasitic ant Solenopsis daguerri is being considered for biological control.

In Brisbane, Australia, colonies have been effectively controlled by ground baiting with food laced with contraceptives and poisons that render the colony's Queen infertile. Mass baiting was undertaken following detection of the ants around the port of Brisbane in 2001. Widespread public reporting of colonies (by sending in samples of ants for identification) allowed mapping of the ant's locations. This was combined with satellite imagery to determine the habitats most likely to be infiltrated by the ants and the baits were targeted in these areas. Some areas were declared high-risk, and any material being moved from these areas which could harbour ants (soil, mulch, potting mix, hay bales, construction machinery) had to be sent to transfer stations for examination, treatment and disposal. The infestation was initially found to cover 27,000 hectares and there was a density of up to 6,000 colonies per hectare. Following the campaign, less than 100 colonies were reported in the entire South-East Queensland area in the 6 months between September 2006 and February 2007. The focus of eradication has switched to surveillance and control measures are expected to continue until 2009. The six year eradication campaign has cost A$175 million