Field experiments conducted in 1991, 1992, and 1993 evaluated Palmer amaranth and devil's-claw control and cotton injury with pyrithiobac applied PPI, PRE, or POST. Pyrithiobac at 36 or 71 g ae/ha applied PPI, PRE, or POST did not injure cotton. Pyrithiobac at 140 g/ha applied PPI or PRE injured cotton 9 to 11% 6 wk after treatment. Cotton recovered and no injury was observed 12 wk after treatment. Pyrithiobac applied PPI and PRE at 71 g/ha controlled Palmer amaranth at least 97% 6 wk after treatment. Palmer amaranth control with pyrithiobac applied POST was more variable and influenced by environmental conditions. Palmer amaranth control with 71 g/ha of pyrithiobac exceeded that with 36 g/ha. Devil's-claw control with pyrithiobac was better with POST applications than PPI or PRE applications. Pyrithiobac applied POST at 140 g/ha controlled devil's-claw 83–97%. These studies indicate that pyrithiobac can effectively control Palmer amaranth and devil's-claw in cotton on the Texas Southern High Plains when applied at appropriate rates and timings.