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Background Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established. Methods For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by the Initiative. To establish a baseline, we conducted censuses of 90,000 households, completed 20,225 household interviews, and surveyed 479 health facilities in the poorest areas of Mesoamerica. Pairing health facility and household surveys allows us to link barriers to care and health outcomes with health system infrastructure components and quality of health services. Results Indicators varied significantly within and between countries. Anemia was most prevalent in Panama and least prevalent in Honduras. Anemia varied by age, with the highest levels observed among children aged 0 to 11 months in all settings. Belize had the highest proportion of institutional deliveries (99%), while Guatemala had the lowest (24%). The proportion of women with four antenatal care visits with a skilled attendant was highest in El Salvador (90%) and the lowest in Guatemala (20%). Availability of contraceptives also varied. The availability of condoms ranged from 83% in Nicaragua to 97% in Honduras. Oral contraceptive pills and injectable contraceptives were available in just 75% of facilities in Panama. IUDs were observed in only 21.5% of facilities surveyed in El Salvador. Conclusions These data provide a baseline of much-needed information for evidence-based action on health throughout Mesoamerica. Our baseline estimates reflect large disparities in health indicators within and between countries and will facilitate the evaluation of interventions and investments deployed in the region over the next three to five years. SM2015’s innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need. Electronic supplementary material The online version of this article (doi:10.1186/s12963-015-0034-4) contains supplementary material, which is available to authorized users.