Two experiments were designed to evaluate the effects of monensin, virginiamycin, and flavomycin on growth performance, carcass characteristics, apparent total tract nutrient digestibility, and rumen fermentation of zebu cattle fed a no-roughage finishing diet (whole shelled corn [WSC] based). In Exp. 1, 100 crossbred bulls (; 392 kg [SD 46.8] average initial BW) were blocked by initial BW in a 101-d feedlot trial. Five treatments were evaluated using 4 pens per treatment (5 bulls/pen): monensin at 30 mg/kg DM, virginiamycin at 25 mg/kg DM, monensin at 20 mg/kg DM plus virginiamycin at 25 mg/kg DM, flavomycin at 4.4 mg/kg DM, and monensin at 20 mg/kg DM plus flavomycin at 2.2 mg/kg DM. There were no differences in growth performance (final BW, ADG, DMI, and G:F; ≥ 0.527) and carcass characteristics (HCW, dressing percent, and 12th-rib fat; ≥ 0.235) among treatments. In Exp. 2, 7 ruminally fistulated steers were used in a 7 × 7 Latin square design to evaluate the 5 treatments of Exp. 1 and 2 additional treatments: monensin at 30 mg/kg DM plus virginiamycin at 25 mg/kg DM and monensin at 20 mg/kg DM plus flavomycin at 4.4 mg/kg DM. Experimental periods were 14 d in length (9 d of adaptation and 5 d of measurements). Apparent total tract DM, OM, CP, and NDF digestibilities were similar among treatments ( ≥ 0.224). There was no treatment effect ( ≥ 0.253) in rumen fermentation responses (ruminal pH, rumen ammonia nitrogen, VFA, and number of protozoa). In conclusion, no evidence of benefits to cattle fed a no-roughage WSC-based diet was found to support the use of monensin combined with virginiamycin or flavomycin in the doses tested herein.