Platelets are critical in inflammation, wound healing, and thrombosis. Platelet count (PLT) and mean platelet volume (MPV) are heritable, frequently assessed measures for which hundreds of genetic associations have been identified, predominantly in European populations. However, causal variants are unknown at most loci, and additional genetic determinants in diverse ancestral populations remain to be discovered. We performed a multi-ancestry whole genome sequencing analysis for PLT in three Phase 1 TOPMed cohorts, the European American Framingham Heart (FHS, n=2259) and Old Order Amish (OOA, n=1095) studies and the African American Jackson Heart Study (JHS, n=3523). MPV was additionally analyzed in JHS and FHS. Heritability in JHS and FHS was 45-73%. Single variant and aggregate burden and sequence kernel association (SKAT) tests [5 and 50 kilobase (kb) sliding windows] were performed using a mixed model approach in GENESIS, with aggregate tests for variants with a minor allele frequency (MAF) < 1% only. Inverse normalized residuals were adjusted for sex, age, study, and an empirical genetic relationship matrix, allowing for heterogeneous variance by study. For PLT, several associations had the same index SNP (ARHGEF3, TPM4) or were in moderate LD (TAOK1, r2=0.46) with a previously reported signal; two associations were not in LD (r2<0.1) with a known locus. The first locus (rs73022249, p=1.2 x 10-8, MAF=16%), an intergenic variant upstream of telomerase reverse transcriptase (TERT), is common only in African ancestry populations (~36%, 1% in Europeans) and was significant only in JHS (p=4.7 x 10-9, p=0.91 FHS, absent OOA). This variant and an LD proxy (rs10052815) overlap a GATA1 binding site in erythroblasts, the sister lineage of platelet producing megakaryocytes. An intronic TERT variant (rs2736100) 17 kb away (r2=0.025, D’=0.418 in included TOPMed cohorts) has been associated with PLT in Europeans, as well as with red blood cell traits, telomere length, pulmonary fibrosis, and multiple cancer subtypes. The second locus (rs73437176, p=1.5 x 10-8, MAF=12%), an intronic variant in progestin and adipoQ receptor family member V (PAQR5), is also more frequent in African ancestry populations (~25%, 4% in Europeans) and significant only in JHS (p=2.5 x 10-8, FHS p=0.47, OOA p=0.12); the nearest previously identified signal is ~4 Mb away and not in significant LD (D’<0.01). Seven known platelet loci were identified for MPV (DNM3, ARHGEF3, CCDC71L, JMJD1C, RHOF, TAOK1, TPM4), with either the same lead variant as previously reported or a variant in close LD (r2>0.75). Aggregated sliding window tests did not identify any additional signals. These results show suggestive evidence for association with PLT for two novel variants common only in African ancestry populations, but larger sample sizes of diverse ancestry will be necessary for replication and further discovery of novel loci.