Pearl millet topcross hybrids (inbred male-sterile seed parent × open-pollinated variety restorer) based on locally adapted varieties and publicly available seed parents provide an ideal entry point into the commercial hybrid seed business, which can stimulate commercial investment by prospective seed producers. To demonstrate this potential, fifteen topcross hybrids made with the widely adapted variety ICMV 221 were evaluated in Eritrea, Sudan and Kenya for overall field performance, and in India for mechanisms of expression of heterosis and for terminal drought tolerance. Across all evaluation environments, the mean yield heterosis was 8%, with a range of −1% to +19%; six hybrids had a statistically significant, positive across-environment yield heterosis (ranging from +11% to +19%). Significant grain yield heterosis in rainy season environments was a consequence of heterosis in both biomass and harvest index, but not necessarily in any specific yield component. Positive grain yield heterosis under terminal drought stress, a common occurrence in millet-growing environments, was related to positive heterosis for grain size. These results are discussed in terms of their support for topcross hybrids as an entry point for prospective millet seed producers, and a scheme presented for the rapid creation, evaluation and marketing of locally adapted topcross hybrids.