Commercial cultivation of Ganoderma species found in Nigeria does not exist. Four Ganoderma isolates (YCT-BKS, YCT-Q2, YCT-Q14, and YCT-Q18) collected in Lagos were tested for mycelia growth and cultivation in sawdust-based substrates. Internal transcribed spacer sequences (ITS1 and ITS4) from three isolates upon a GenBank BLAST search gave DNA sequence closest identities as YCT-BKS and YCT-Q14 = G. mbrekobenum and YCT-Q2 = G. enigmaticum. The mycelia growth rate was highest in YCT-BKS (1.2 cm/day), whereas the other three isolates averaged 0.7 cm/day. On substrate A (sawdust/water hyacinth, 7:3), the time to form primordia was 30 days for YCT-BKS, YCT-Q18, and YCT-Q14. YCT-Q2 and YCT-Q18 formed primordia (27 days) on substrate B (sawdust/sorghum, 3:2). YCT-BKS was the first to produce basidiocarp on substrate A (75 days after inoculation) and had the highest biological efficiency (BE) of 13.4%, followed by YCT-Q18 with BE of 12.1% on substrate B after 99 days. YCT-Q14 produced fruiting bodies after 92 days on substrate A, with a low BE of 7.0%. Results indicate the need to supplement sawdust (substrate C = 100% sawdust) to cultivate the Ganoderma spp. A mixture of sawdust and water hyacinth appears to be the best substrate among those tested. This is the first report on the domestication and cultivation of indigenous isolates of Ganoderma spp. from Nigeria on sawdust and water hyacinth. Water hyacinth is a noxious weed causing major problems in fresh waterways in Nigeria.