Reduced control of some glyphosate-resistant hairy fleabane populations with paraquat has raised concerns about evolved multiple resistance to both glyphosate and paraquat. The objective of this study was to confirm the presence of multiple-resistant (glyphosate and paraquat) hairy fleabane populations in California. A series of dose-response experiments was conducted to evaluate the effect of glyphosate and paraquat in a known susceptible (S) and putative multiple-resistant (R) population of hairy fleabane. The greenhouse experiments were conducted during summer, fall, and winter under controlled temperature and natural light conditions. Multiple-resistant hairy fleabane was identified; however, the level of resistance to glyphosate varied substantially among seasons. During the summer, the glyphosate rate required to reduce growth by 50% (GR50) for the R population was 0.94 kg ae ha−1, 5.2-fold more than for the S population. In the fall and winter experiments, however, the R population response to glyphosate was similar to the S population with a GR50 of 0.22 kg ae ha−1 or less. Multiple-resistant plants were controlled in the fall and winter at rates that did not control the same population during summer. GR50 of paraquat varied among seasons (0.94, 0.24, and 0.07 kg ai ha−1 during summer, fall, and winter, respectively); however, plant mortality was more consistent. This is the first reported case of glyphosate–paraquat resistance in hairy fleabane and the multiple-resistant population could pose a significant challenge to annual no-till and perennial cropping systems in California. Further research on the mechanisms of resistance and the physiological factors underlying the seasonally variable response to glyphosate is needed.