If the predominant means of HIV transmission is heterosexual in the Soconusco region of Mexico, then the female sex workers (FSWs) from Central America who work in this region may be playing a significant role in the heterosexual transmission of HIV. The goal was to estimate the prevalence of several sexually transmitted infections (STIs), including HIV infection, and to evaluate the population mobility of Mexican and Central American FSWs in the Soconusco region in Chiapas State, Mexico. A cross-sectional study was conducted upon the construction of a sampling frame of sex work-related bars in the municipalities of the Soconusco region. Consenting participants answered a questionnaire that recorded sociodemographic characteristics, previous and current experience in commercial sex, and risk indicators for STI. Women also provided blood and endocervical swab specimens to be analyzed. A sample of 484 women were enrolled, who were characterized as follows: the average age was 25.6 years, and a high proportion had children, were single, had started sexual activity at an early age, and had a low level of education and low earnings. The global prevalences of infections with Treponema pallidum, HSV-2, HIV, Neisseria gonorrhoeae, and Chlamydia trachomatis were 9.4%, 85.7%, 0.6%, 11.6%, and 14.4%, respectively. Frequencies of HBcAb and HBsAg hepatitis B markers were 17.7% and 1.3%. The cumulative prevalence of treatable gonorrhea, chlamydia, and syphilis was 27.4%. The data on women's mobility illustrate that the Soconusco region attracts Central American women to enter the commercial sex trade. The women's sociodemographic characteristics were consistent with high prevalences of STI, except HIV infection. The low frequency of HIV infection suggests that this population may have had little contact with HIV core groups in Central America and in the Soconusco and no history of blood transfusion or intravenous drug use.