Karnal bunt caused by Tilletia indica Mitra [syn. Neovossia indica (Mitra) Mundkur] is a significant biosecurity concern for wheat-exporting countries that are free of the disease. It is a seed-, soil-and air-borne disease with no effective chemical control measures. The current study used data from multi-year field experiments of two bi-parental populations and a genome-wide association (GWA) mapping panel to unravel the genetic basis for resistance in common wheat. Broad-sense heritability for Karnal bunt resistance in the populations varied from 0.52 in the WH542×HD29 population, to 0.61 in the WH542×W485 cross and 0.71 in a GWAS panel. Quantitative trait locus (QTL) analysis with seven years of phenotypic data identified a major locus on chromosome 3B (R2 = 27.8%) and a minor locus on chromosome 1A (R2 = 12.2%), in the WH542×HD29 population, with both parents contributing the high-value alleles. A major locus (R2 = 27.8%) and seven minor loci (R2 = 4.4–15.8%) were detected in the WH542×W485 population. GWA mapping validated QTL regions in the bi-parent populations, but also identified novel loci not previously associated with Karnal bunt resistance. Meta-QTL analysis aligned the results from this study with those reported in wheat over the last two decades. Two major clusters were detected, the first on chromosome 4B, which clustered with Qkb.ksu-4B, QKb.cimmyt-4BL, Qkb.cim-4BL, and the second on chromosome 3B, which clustered with Qkb.cnl-3B, QKb.cimmyt-3BS and Qkb.cim-3BS1. The results provide definitive chromosomal assignments for QTL/genes controlling Karnal bunt resistance in common wheat, and will be useful in pre-emptive breeding against the pathogen in wheat-producing areas that are free of the disease.