The ecological responses of large rivers to human pressure can be assessed at multiple scales using a variety of indicators, but little is known about how the responses of ecological indicators vary over small spatial scales. We sampled phytoplankton, zooplankton and macroinvertebrates and measured river metabolism and cotton strip breakdown rates (loss in tensile strength) in contrasting habitats along a 21-km urban-industrial reach on a constrained section of the Waikato River, New Zealand's longest river. Rates of gross primary production (2.8–7.8 g O2/m2/d) and ecosystem respiration (3.5–12.7 g O2/m2/d) did not differ consistently between near-shore (2–3 m from river side) and far-shore (ca. 10 m from side) locations, urban and industrial reaches or between autumn and spring sampling occasions. Rates of cotton decay (−k) ranged from 0.014 to 0.112 per day and were typically faster at far-shore locations and in the section of river receiving industrial inputs, but slower in spring compared with autumn. Nonmetric multidimensional scaling analysis of phytoplankton and zooplankton data did not reveal spatial patterns relating to pressure or location (embayment, edge, mid-river). However, the macroinvertebrate ordination suggested distinct communities for the mid-river benthos compared with near-shore communities and a distinction between sites in the urban reach and the industrial reach. Our results suggest that large-river macroinvertebrate communities and cotton decay rates can be influenced to varying degrees by reach-scale pressures and local habitat conditions. Monitoring designs in spatially complex rivers should account for habitat heterogeneity that can lead to differences in structural and functional indicator responses.