While a rising prevalence of anemia in the United States was reported in older studies, recent data are lacking. To estimate the prevalence and time trends of anemia in the United States and to examine how these estimates differ by gender, age, race, and household income to poverty threshold ratio (HIPR), we used the National Health and Nutrition Examination Surveys from 1999 to 2020. The presence of anemia was determined using the World Health Organization criteria. Survey-weighted raw and adjusted prevalence ratios (PRs) were determined using generalized linear models for the overall population and by gender, age, race, and HIPR. In addition, an interaction between gender and race was explored. Complete data on anemia, age, gender, and race were available on 87,554 participants (mean age = 34.6 years, women = 49.8%, Whites = 37.3%). Anemia prevalence increased from 4.03% during the 1999–2000 survey cycle to 6.49% during 2017–2020. In adjusted analyses, anemia prevalence was higher in >65 than in 26–45 years old (PR = 2.14, 95% confidence interval (CI) = 1.95, 2.35), in Blacks than Whites (PR = 3.97, 95% CI = 3.63, 4.35), in women than men (PR = 1.98, 95% CI = 1.83, 2.13), and in those with HIPR ≤ 1 than >4 (PR = 0.68, 95% CI = 0.61, 0.75). Gender modified the relationship between anemia and race; when compared to their male counterparts, Black, Hispanic, and other women had higher anemia prevalence than White women (all interaction p values <0.05). The anemia prevalence in the United States has risen from 1999 to 2020 and remains high among the elderly, minorities, and women. The difference in anemia prevalence between men and women is larger in non-Whites.