The scientific name of the common species is Cavia porcellus, with porcellus being Latin for "little pig". Cavia is New Latin; it is derived from cabiai, the animal's name in the language of the Galibi tribes once native to French Guiana.  Cabiai may be an adaptation of the Portuguese çavia (now savia), which is itself derived from the Tupiword saujá, meaning rat.  

Guinea pigs are called quwi or jaca in Quechua and cuy or cuyo (plural cuyes, cuyos) in the Spanish of Ecuador, Peru, and Bolivia.  Ironically, breeders tend to use the more formal "cavy" to describe the animal, while in scientific and laboratory contexts, it is far more commonly referred to by the more colloquial "guinea pig".

The animal's name alludes to pigs in many European languages. The German word for them is Meerschweinchen, literally "little sea pig", which has been translated intoPolish as świnka morska, into Hungarian as tengerimalac, and into Russian as морская свинка. This derives from the Middle High German name merswin. This originally meant "dolphin" and was used because of the animals' grunting sounds (which were thought to be similar).

 Many other, possibly less scientifically based explanations of the German name exist. For example, sailing ships stopping to reprovision in the New World would pick up stores of guinea pigs, which provided an easily transportable source of fresh meat. The French term is cochon d'Inde (Indian pig) or cobaye; the Dutch call it Guinees biggetje (Guinean piglet) or cavia (while in some Dutch dialects it is called Spaanse rat); and in Portuguese, the guinea pig is variously referred to as cobaia, from the Tupi word via its Latinization, or as porquinho da Índia (little Indian pig). This is not universal; for example, the common word in Spanish is conejillo de Indias (little rabbit of the Indies). The Chinese refer to them as 豚鼠 (túnshǔ, 'pig mouse'), and sometimes as Netherlands pig (荷蘭豬, hélánzhū) or Indian mouse (天竺鼠, tiānzhúshǔ).

The Japanese word for guinea pig is "モルモット" (morumotto), which derives from the name of another mountain-dwelling rodent, the marmot; this is what guinea pigs were called by the Dutch traders who first brought them to Nagasaki in 1843.

The origin of "guinea" in "guinea pig" is harder to explain. One proposed explanation is that the animals were brought to Europe by way of Guinea, leading people to think they had originated there.  "Guinea" was also frequently used in English to refer generally to any far-off, unknown country, so the name may simply be a colorful reference to the animal's exotic appeal.

Another hypothesis suggests the "guinea" in the name is a corruption of "Guiana", an area in South America, though the animals are not native to that region.   A common misconception is that they were so named because they were sold for the price of a guinea coin; this hypothesis is untenable, because the guinea was first struck in England in 1663, and William Harvey used the term "Ginny-pig" as early as 1653.   Others believe "guinea" may be an alteration of the word coney (rabbit); guinea pigs were referred to as "pig coneys" in Edward Topsell's 1607 treatise on quadrupeds.