Agricultural runoff is a major contributor of nutrients to downstream freshwater and marine waters that, in turn, cause harmful algal blooms. “Wetlaculture,” a new landscape management approach defined as “integrating wetland nutrient removal with recycling of these nutrients to agriculture,” has the dual goals of reducing the need for fertilizer in agriculture while mitigating fluxes of nutrients to downstream aquatic ecosystems with created or restored wetlands. A mesocosm compound consisted of twenty-eight 380 L, 1-m2 tubs filled with local hydric soil was initiated in mid-2016 near a highly eutrophic Buckeye Lake in central Ohio, USA, to investigate the wetlaculture approach in an experimental fashion. In October 2016, each mesocosm tub was inserted in the ground and planted with the sedge Schoenoplectus tabernaemontani. The mesocosms were assigned to four hydrologic treatments involving two water depths and two hydraulic loading rates (HLRs). Nearby river water containing significant agricultural runoff was added weekly into a water feed tank system to provide weekly hydraulic loadings to the mesocosms. Inflow and outflow water samples from each wetland mesocosm were collected and analyzed for five species of nitrogen and phosphorus. By August 2019, 17 plant species, including the planted S. tabernaemontani, were present in the wetland mesocosms. The wetland mesocosms soon became nutrient sinks with average removal efficiencies of total phosphorus (TP) and total nitrogen (TN) of 38 ± 2.5% and 44 ± 1%, respectively, through the three-year experiment. The combination of a high HLR (30 cm week−1) and 10 cm of standing water achieved the best nitrogen removal efficiencies while highest phosphorus removal occurred with the combination of a high HLR (30 cm week−1) and no standing water.This paper discusses the following integrative findings:•Seasonal flooding had positive impacts on removal efficiency of NOx and a negative impact on the removal efficiency of TP and TKN.•No standing water resulted in a higher removal efficiency of TP and TKN than standing water, results consistent with previous studies.•Macrophyte plant community richness was influenced more by water depth than by hydraulic loading rate. Wetlands with 10 cm of standing water instead of saturated soils developed lower species richness but were more dominated by true wetland (OBL and FACW) species.•Study scale does matter. Annual nutrient accumulation rates in the mesocosms (1 m2) soils were lower than in the full-scale (10,000-m2) multi-year wetlands at the nearby Olentangy River Wetland Research Park (ORWRP) in central Ohio. Annual accumulation rates of phosphorus and nitrogen in the full-scale wetlands ranged from 3.3 to 3.5 g-P m−2 yr−1 and 16.4 to 19.5 g-N m−2 yr−1, while in our mesocosms, the annual rates ranged from 0.66 to 1.40 g-P m−2 yr−1 and 7.85 to 15.08 g-N m−2 yr−1. Our experimental wetland mesocosms could only function in the non-freezing months and have been in operation for only three years.