The invasion of nonnative grasses threatens biodiversity and ecosystem function globally through competition with native plant species and increases to wildfire frequency and intensity. Management actions to reduce buffelgrass [Pennisetum ciliare (L.) Link], an invasive warm-season perennial bunchgrass, are widely implemented, with chemical and mechanical treatments extending over two decades within Saguaro National Park in the Sonoran Desert of North America. We assessed how the effectiveness of treatments to reduce P. ciliare cover spanning from 2011 to 2020 were influenced by stage of invasion, treatment type and intensity, and environmental conditions. An increase in treatment effectiveness was largely explained by high initial cover of P. ciliare, an indicator of a late invasion stage and associated with high treatment intensity. Treatments had potential to be effective in patches as small as 0.3-m2 P. ciliare canopy per 400-m−2 area (<0.001% canopy cover) across treatment types and environmental gradients. Chemical treatments had higher or equal effectiveness compared with mechanical treatments, and greater reductions in P. ciliare were associated with shorter average years of treatment interruptions, or gaps, and to a lesser degree, total years of treatment. In many cases, P. ciliare was reduced with as little as 2 yr of treatment, but more than 3 average years of treatment gap could result in reduced treatment effectiveness. There was generally higher treatment effectiveness on shallow slopes, north- and east-facing aspects, and on higher elevations within one district of the park. Our findings highlight that resource-intensive treatments in all but the smallest patches of P. ciliare have largely been effective. Further opportunities for improvement include more frequent surveillance, limiting treatment gaps to ≤3 yr in areas of low P. ciliare cover, and comparison of treated with untreated areas.