The occurrences of equatorial plasma bubble (EPB) irregularities over Asian and American sectors often show a different behavior due to significantly different geometries of the geomagnetic field. By using the GPS total electron content observations over equatorial and low latitudes sectors of Asian (about 120°E) and American (about 60°W) during 1997–2018, we present a comparative study of long-term occurrences of EPB kilometer-scale irregularities over the two longitude sectors. The results show that post-sunset EPB irregularities over the Asian sector were positively correlated with solar activity. However, in the American sector, such a positive dependence was not apparent in 2000–2002, which could be partly induced by limited data available during the high occurrence season of solar maximum when the GPS receivers frequently lost lock. The geomagnetic disturbance tends to inhibit the generation of EPB irregularities over both sectors during post-sunset but enhance their generation during post-midnight. The latitudinal distribution of EPB irregularities exhibited a double-peak structure centered within ± 10° (dip lat.), with the latitudinal limit below ± 25° at solar maximum in both sectors and below ± 20° and ± 10° at solar minimum in American and Asian sectors, respectively. Specifically, in the American sector, the occurrence rates were about two times higher than those in the Asian sector, and the occurrence rates in the northern hemisphere were apparently lower than those in the southern hemisphere. The enhanced ionization by particle precipitation over the South Atlantic Magnetic Anomaly region could cause the north–south asymmetry of occurrence rates of EPB irregularities. The results help in designing experiments to understand better the generation of EPB irregularities under the future international meridian circle project.