The question of whether species co-occurrence is random or deterministic has received considerable attention, but little is known about how anthropogenic disturbance mediates the outcomes. By combining experiments, field surveys and analysis against null models, we tested the hypothesis that anthropogenic habitat modification disrupts species co-occurrence in stream invertebrates across spatial scales. Whereas communities in unmodified conditions were structured deterministically with significant species segregation, catchment-scale conversion to agriculture and sediment deposition at the patch- or micro-habitat scale apparently randomized species co-occurrences. This shift from non-random to random was mostly independent of species richness, abundance and spatial scale. Data on community-wide life-history traits (body size, dispersal ability and predatory habits) and beta-diversity indicated that anthropogenic modification disrupted community assembly by affecting biotic interactions and, to a lesser extent, altering habitat heterogeneity. These data illustrate that the balance between predictable and stochastic patterns in communities can reflect anthropogenic modifications that not only transcend scales but also change the relative forces that determine species coexistence. Research into the effects of habitat modification as a key to understanding global change should extend beyond species richness and composition to include species co-occurrence, species interactions and any functional consequences.