An important limitation to cotton (Gossypium hirsutum L.) production in the Texas High Plains is water shortage. A 2-yr study was conducted at two locations in Lubbock, TX, in 2007 and 2008 to determine the optimal irrigation and plant density for cotton production in the Texas High Plains based on yield and fiber quality. A field experiment was conducted by using a split plot design, with irrigation (0, 2.54 and 5.08 mm d-1) as the main plot, and plant density (75,300; 150,600; and 226,000 plants ha-1) as the subplot. Two central rows of each plot were machine harvested to determine lint yield. Fiber quality was tested by both High Volume Instrument (HVI) and Advanced Fiber Information Systems (AFIS). The results showed environmental conditions heavily impact lint yield and fiber quality. Irrigation played a significant role in yield and fiber quality. Under appropriate weather conditions at Quaker 2008, 5.08 mm d-1 irrigation rate increased seed cotton yield by 36.4 and 214.3%, compared with 2.54 and 0 mm d-1, respectively. Irrigation of 5.08 mm d-1 increased fiber length by number, uniformity, and short fiber content. The fineness and maturity ratio and subsequently micronaire decreased. Plant density seemed to play a smaller role in determining yield and fiber quality. Based on profitability, higher yield did not necessarily translate to higher net returns. We concluded that weather pattern and irrigation heavily impact yield and fiber quality in the Texas High Plains.