The flocculation–column flotation with hydraulic loading (HL, >10 m h−1) was studied for the treatment of oil-in-water emulsions containing 70–400 mg L−1 (turbidity = 70–226 NTU) of oil and salinity (30 and 100 g L−1). A polyacrylamide (Dismulgan, 20 mg L−1) flocculated the oil droplets, using two floc generator reactors, with rapid and slow mixing stages (head loss = 0.9 to 3.5 bar). Flotation was conducted in two cells (1.5 and 2.5 m) with microbubbles (MBs, 5–80 μm) and nanobubbles (NBs, 50–300 nm diameter, concentration of 108 NBs mL−1). Bubbles were formed using a centrifugal multiphase pump, with optimized parameters and a needle valve. The results showed higher efficiency with the taller column reducing the residual oil content to 4 mg L−1 and turbidity to 7 NTU. At high HL (27.5 m h−1), the residual oil concentrations were below the standard emission (29 mg L−1), reaching 18 mg L−1. The best results were obtained with high concentration of NBs (apart from the bigger bubbles). Mechanisms involved appear to be attachment and entrapment of the NBs onto and inside the flocs. Thus, the aggregates were readily captured, by bigger bubbles (mostly MBs) aiding shear withstanding. Advantages are the small footprint of the cells, low residence time and high processing rate.