Higher plant population and nitrogen management is an adopted approach for improving crop productivity from limited land resources. Moreover, higher plant density and nitrogen regimes may increase the risk of stalk lodging, which is a consequence of complex interplant competition of individual organs. Here, we aimed to investigate the dynamic change in morphology, chemical compositions and lignin promoting enzymes of the second basal inter-nodes altering lodging risk controlled by planting density and nitrogen levels. A field trial was conducted at the Mengcheng research station (33°9′44″N, 116°32′56″E), Huaibei plain, Anhui province, China. A randomized complete block design was adopted, in which four plant densities, i.e., 180, 240, 300, and 360 × 104 ha−1 and four N levels, i.e., 0, 180, 240, and 300 kg ha−1 were studied. The two popular wheat varieties AnNong0711 and YanNong19 were cultivated. Results revealed that the culm lodging resistance (CLRI) index of the second basal internodes was positively and significantly correlated with light interception, lignin and cellulose content. The lignin and cellulose contents were significantly and positive correlated to light interception. The increased planting density and nitrogen levels declined the lignin and its related enzymes activities. The variety AnNong0711 showed more resistive response to lodging compared to YanNong19. Overall our study found that increased planting densities and nitrogen regimes resulted in poor physical strength and enzymatic activity which enhanced lodging risk in wheat varieties. The current study demonstrated that stem bending strength of the basal internode was significantly positive correlated to grains per spike. The thousand grain weight and grain yield had a positive and significant relationship with stem bending strength of the basal internode. The results suggested that the variety YanNong19 produces higher grain yield (9298 kg ha−1) at density 240 × 104 plants ha−1, and 180 kg ha−1 nitrogen, while AnNong0711 produced higher grain yield (10178.86 kg ha−1) at density 240 × 104 plants ha−1 and with 240 kg ha−1 nitrogen. Moreover, this combination of nitrogen and planting density enhanced the grain yield with better lodging resistance.