Integration of different weed control methods is essential to address the financial as well as environmental concerns being faced by nursery and landscape industry. Herbicide and mulch combinations have been suggested to achieve longer weed control in nurseries and landscapes. Field and laboratory experiments were conducted to determine the effects of herbicide formulations, mulch materials, depths of mulches, and herbicide placement relative to mulches on herbicide efficacy and persistence. Two field experiments were conducted, the first in the fall of 2006 and 2007 and the second in spring of 2007 and 2008. Granular and liquid formulations of a trifluralin+isoxaben mixture were applied alone and in combination with pine nuggets and hardwood mulch at three depths, 3-, 6-, and 12-cm. Granular herbicides were applied alone (without mulch) and above the mulch; and granular-pretreated mulches were also included. Liquid herbicides were applied alone, over the mulch, under the mulch, or as herbicide-pretreated mulches. Trifluralin and isoxaben in all formulations were applied at the rate of 4.48 kg ai/ha + 1.12 kg ai/ha, respectively. Mulch alone treatments and untreated control (no mulch, no herbicide) were also included. Visual weed control ratings and weed fresh weight data were collected at 30, 60, 90, and 120 days after treatment (DAT) for the spring experiment and at 180 and 210 DAT for the fall experiment. Visual ratings were based on a scale of 0 (no control) to 10 (complete control), with 7 and above being commercially acceptable. Selected treatments from the spring experiment, including the granular formulation alone, the liquid formulation alone, liquid formulation applied under 6-cm mulches, and the liquid formulation-treated mulches at 6-cm were used to investigate herbicide persistence. Herbicide residue analysis using liquid chromatography and bioassay studies using oats and radish were part of the herbicide persistence studies. All the treatments involving 6-cm and 12-cm mulch with or without herbicides provided efficacy ratings of above 7 in both experiments. Certain combinations of 3-cm mulch and herbicides, such as granular formulation over 3-cm pine nuggets, liquid formulation under 3-cm pine nuggets, and liquid formulation under 3-cm hardwood consistently provided at efficacy ratings ≥ 7 at all evaluation dates in both studies. This could be due to the longer residual activity of herbicides in those treatments. The time-course assay of herbicide dissipation in soil indicated that herbicides applied under the mulch persisted longer compared to herbicides applied alone. Results suggested that the persistence of herbicides largely depended on the physico-chemical properties of herbicides and mulches, as well as soil moisture and temperature. Weed control with greater mulch thickness could be largely due to the physical inhibition of weed germination and growth by the mulch, whereas at lower mulch thickness, the addition of herbicides to the mulch treatments was necessary to provide weed control equivalent to the thick mulch layer. Mulches applied at the 12-cm depth are expensive and can be detrimental to health of desirable plants, even though it provided almost complete weed control. Depth of mulches could be reduced to 3-cm from commercially recommended depths of 5- to 8-cm when herbicides were combined with mulches.