Background: Multiple Myeloma (MM) is a plasma cell malignancy due to proliferation of malignant clonal plasma cells. Prior studies have shown that overall incidence of MM was 8.47 per 100,000 individuals. It has also been seen that the incidence of MM has trended upwards in non-Hispanic white (NHW) males and non-Hispanic blacks (NHB) across all age groups. This retrospective, database-driven population study sought to further assess racial and gender-based differences in the trends of the incidence of MM and mortality from MM. Methods: Data obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry 17 were available to assess trends of multiple myeloma incidence and mortality from 2000 to 2019. Trends were described as average annual percentage change (APC) rates. Results: A total of 102,467 MM patients were identified in this data set; 56,508 (55.1%) were males and 45,949 (44.8%) were female. The distribution of MM by race was as follows (in order from highest to lowest): Non-Hispanic White [NHW] patients was 63.2% (N = 64,776), Non-Hispanic Black [NHB] patients was 18.6% (n = 19,099), Hispanic patients was 11.6 % (11,841), Non-Hispanic Asian [NHA] patients was 5.6% (5,769), and Non-Hispanic American Indian [NHAI]/Alaska Native patients was 0.5% (523). Incidence of MM (cases per 100,000 persons) was highest in males (7.5; 95% CI: 7.5, 7.6) and blacks (13; 95% CI: 12.8, 13.2). Overall trend in the incidence of MM has increased significantly for all gender and ethnicity groups over the period from 2000-2019, except for NHA patients. The incidence-based mortality of MM was highest in male (5.2; 95% CI: 5.2, 5.3) and black (8.7; 95% CI: 8.5, 8.8) patients. The overall incidence-based mortality increased significantly in males APC 4.1% (95% CI: 2.2,5.9; p < 0.001), females APC 3.6% (95% CI, 1.8,5.5; p < 0.001) and all ethnicities - NHW patients APC 4.1%, (95% CI, 2.2,6.0; p < 0.001), NHB (APC 4.2%, 95% CI, 2.1,6.3; P < 0.001), NHAI (APC 4.7%, 95% CI, -2.2,7.2; p < 0.001), NHA (APC 3.0%, 95% CI: 0.8,5.2; P = 0.009) and Hispanic (APC 2.9, 95% CI:1.1,4.7; P = 0.003). Conclusions: Population-based trends in MM incidence and mortality, as reported in this study, were increased commensurate with prior reports. Of note, mortality was noted to be highest amongst the NHB and male populations, indicating a need for further research focused efforts in this potentially high-risk population.