HIV incidence in the USA is three times higher for Latinos than for non-Latino whites. Latinos differ in educational attainment, poverty, insurance coverage, and health-care access, factors that affect HIV knowledge, risk behaviors, and testing. The purpose of this study was to identify differences in demographics, risk factors, and rate of new HIV diagnoses by birth country/region among Latinos in Florida to guide the targeting of primary and secondary prevention programs. Using Florida HIV/AIDS surveillance data from 2007 to 2011 and the American Community Survey, we compared demographic and risk factors, and calculated annual and five-year age-adjusted rates of new HIV diagnoses for 5801 Latinos by birth country/region. Compared to US-born Latinos, those born in Cuba and South America were significantly more likely to report the HIV transmission mode of MSM; those born in the Dominican Republic (DR) heterosexual transmission; and those born in Puerto Rico injection drug use. Mexican- and Central American-born Latinos were more likely to be diagnosed with AIDS within a month of HIV diagnosis. The rate of new HIV diagnoses among Latinos declined 33% from 2007 to 2011. HIV diagnoses over time decreased significantly for Latinos born in Mexico and increased nonsignificantly for those born in the DR. Although this study was limited to Latinos living in Florida, results suggest that tailoring HIV primary prevention and testing initiatives to specific Latino groups may be warranted.