Reducing tillage has become necessary in irrigated, arid cropping systems in southwestern USA, to address soil degradation and erosion problems associated with intensive soil tillage. A study was conducted in arid southwestern USA, to compare a reduced tillage method (strip tillage) to two conventional tillage methods (plow tillage and raised bed tillage) for irrigated upland cotton (Gossypium hirsutum) production. Strip tillage (ST) was established in a single pass by a strip tillage equipment, while the plow tillage (PT) consisted of plowing, disking the soil twice, subsoiling and harrowing. The raised bed tillage (BT) consisted of all the tillage operations under PT method, with an additional tillage event to shape the beds. Crop and soil parameters were assessed during the growing seasons. Soil physical and biological measurements were assessed at the beginning of the trial before planting, and at the end of each cropping season. Results show no significant differences in cotton yield and fiber quality parameters under the tillage systems tested. Out of the soil physical measurements assessed, the cone index (CI) significantly differed with tillage systems during the mid-season assessments, with BT generally having better CI than ST and PT. Other physical measurements were not significant with tillage, but significantly declined over time irrespective of tillage treatments. Out of the soil biological measurements assessed, the total fungal biomass and the arbuscular mycorrhizae fungi biomass were significant with tillage, with ST and BT having higher measurements than PT. In contrast to soil physical measurements that declined, most of the soil biological measurements improved over time. Comparing some soil biological measurements at the beginning to the end of the trial across the tillage treatments, the total microbial biomass increased from 714 to 3565 ng/g, the total bacterial biomass increased from 321 to 1478 ng/g, and the total fungal biomass increased from 84 to 436 ng/g. This study shows that ST can perform adequately for sustainable cotton production in an irrigated arid region of United States.