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Cereal crops have a high N requirement in a high‐yield environment. However, N use efficiency is still low in agricultural production systems and little is known about the effects of inoculation with Azospirillum brasilense in a high‐yield environment. A field experiment was conducted from 2012 to 2018 with a maize (Zea mays L.)–wheat (Triticum aestivum L.) rotation under a continuous no‐till in southern Brazil. Seeds were inoculated with A. brasilense (strains Ab‐V5 and Ab‐V6) and different levels of N fertilization were used in top dressing. Seed inoculation provided slight changes in N, P, and K concentrations in leaves and grains of maize and wheat. Increasing N input increased the leaf and grain N concentration and the maize and wheat grain yields. Seed inoculation caused varied responses on cereals in different cropping seasons. Wheat was more affected by inoculation in response to N application than maize. Rainfall distribution during the growing seasons possibly interfered on crop responses with inoculation between years and N fertilization levels. Under a similar N input, inoculation resulted in an average increase of 454 kg ha−1 yr−1 of maize and 242 kg ha−1 yr−1 of wheat by applying a higher N rate to the maize and a lower N rate to the wheat. An additional gain of US$409.72 ha−1 (2012–2018) was also achieved using this strategy. Although the possibility of inoculation causing economy with N fertilization in wheat was evident, for maize in rotation with wheat, A. brasilense inoculation was apparently more viable under higher N fertilizer input.