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Southern root‐knot nematode (SRKN) is one of the most yield‐suppressing pathogens in soybean [(Glycine max(L.) Merr.] in the United States. With limited chemical and cultural management options, the use of genetic resistance is the most efficient and economical approach to control SRKN. A major quantitative trait locus (QTL) mapped to chromosome 10 is the primary source of resistance in soybean cultivars; however, limited studies have been conducted to evaluate its efficacy in minimizing yield suppression under field conditions with SRKN pressure. This study evaluated the yield performance of 202 elite soybean lines in field conditions with variable distribution of SRKN. Soybean lines were characterized based on the presence of the major QTL on chromosome 10 and grown in four‐row yield plots across six environments over 2 yr. Plots were soil sampled and enumerated to determine nematode population densities. No statistically significant differences in yield performance between resistant and susceptible lines were observed in the absence of nematode pressure, indicating no yield drag associated with resistance. Under SRKN pressure, the group of resistant lines yielded, on average, 19.1 and 23.3% higher than the susceptible lines in 2018 and 2019, respectively. For the susceptible lines, the presence of 1,000 SRKN second‐stage juveniles (J2) in 100 cm−3of soil negatively affected yield by 6.2%. The presence of the major resistance allele on chromosome 10 reduced yield losses by approximately six‐fold in comparison to the susceptible group which provided significant yield protection under high SRKN pressure.