Changes in the physical environment associated with eastern Pacific (EP)-El Niño and central Pacific (CP)-El Niño events affect the biological response in the equatorial Pacific Ocean differently. However, such responses have not been adequately investigated, especially in terms of the relevant physical processes. This paper addresses the mechanistic differences in the biological response of the equatorial Pacific Ocean during the strongest CP- and EP-El Niño to date (i.e., 1997–98 EP-El Niño and 2009–10 CP-El Niño) using satellite data and water mass pathway analysis based on an ocean reanalysis product. The 1997–98 EP-El Niño was associated with a larger reduction of chlorophyll-a (chl-a) in the eastern equatorial Pacific (EEP) and the 2009–10 CP-El Niño was associated with a larger reduction of chl-a in the central equatorial Pacific (CEP). These biological responses were dependent on the strength and extent of westerly wind anomalies and their impact on horizontal and vertical processes. Horizontal advection was the primary contributor to differences in chl-a between the two El Niño events in the CEP, whereas vertical advection and mixing were the dominant processes in the EEP.