This manuscript sets forth an in-depth study of competing pairs of prefixes of Greek and Latin origin: hyper- vs. super-, micro- vs. mini-, and polyvs. multi- from a contrastive Spanish-English perspective. Two major source corpora, the Corpus de Referencia del Español Actual for Spanish, and the British National Corpus for English were used for the purpose of this research. The prefixes were further analysed within the framework of a corpus of 200 translational equivalences, compiled from a lexicographic bilingual source, the Oxford Spanish Dictionary (2003); the results were then corroborated with the use of the prefixed words in a bilingual text-based online source, Linguee. This research sheds light on similarities and differences between such pairs of prefixes. The present contribution confirms the higher use of prefixation in Spanish. A much more frequent use of Latin prefixes, mainly super- and multi-, is attested in both languages. The cross-linguistic study reveals that prefixes seem to overlap semantically and syntactically across Spanish and English. Nevertheless, a representative percentage of Spanish prefixed words contrastively exhibit a non-morphological equivalence in English. Hence, a single different word, or a multiword unit may be used in English where derivational expansion of the base is preferred in Spanish