Behavioral lifestyle interventions during pregnancy can prevent excessive gestational weight gain (GWG) in women with normal weight; however, effective interventions to reduce GWG in ethnically diverse women with obesity are lacking. A randomized controlled trial was conducted to test whether a behavioral lifestyle intervention with partial meal replacement reduces GWG rate in Hispanic and non-Hispanic women with overweight or obesity relative to enhanced usual care. Participants (n=257) were recruited in San Luis Obispo, California, and Providence, Rhode Island, between November 2012 and May 2016. Participants were pregnant (mean ± SD: 13.6 ± 1.8 wk of gestation) with overweight or obesity and had a mean age of 30.3 y; 41.6% of participants were Hispanic. Women were randomly assigned within site and by ethnicity to enhanced usual care (n=128) or to a behavioral lifestyle intervention with partial meal replacement (n=129). The primary outcome was GWG per week of observation. Secondary outcomes were proportions exceeding Institute of Medicine (IOM) guidelines for total GWG, changes in weight-control behaviors and cardiovascular disease risk factors, and incidence of pregnancy complications. Study retention was 99.6% (256 of 257). The intervention compared with usual care resulted in less mean ± SD weekly GWG (0.33 ± 0.25 compared with 0.39 ± 0.23 kg/wk; P=0.02) and total GWG (9.4 ± 6.9 compared with 11.2 ± 7.0 kg; P=0.03) and reduced the proportion of women who exceeded IOM guidelines for total GWG (41.1% compared with 53.9%; P=0.03). No significant group × time × demographic subgroup (ethnicity, BMI, age, parity, and income) interactions were observed. Among intervention participants, greater meal replacement intake was related to reduced GWG rate (β=-0.07; 95% CI:-0.12, -0.03; P=0.002). The intervention compared with usual care increased weight-control strategies (P<0.0001) and cognitive restraint (P<0.0001) and reduced triglycerides (P=0.03). Prenatal behavioral intervention with partial meal replacement significantly reduced GWG in Hispanic and non-Hispanic women with overweight or obesity. This trial was registered at www.clinicaltrials.gov as NCT01545934.