Genomewide association studies have contributed immensely to our understanding of the genetic basis of complex traits. One major conclusion arising from these studies is that most traits are controlled by many loci of small effect, confirming the infinitesimal model of quantitative genetics. A popular approach to test for polygenic architecture involves so‐called “chromosome partitioning” where phenotypic variance explained by each chromosome is regressed on the size of the chromosome. First developed for humans, this has now been repeatedly used in other species, but there has been no evaluation of the suitability of this method in species that can differ in their genome characteristics such as number and size of chromosomes. Nor has the influence of sample size, heritability of the trait, effect size distribution of loci controlling the trait or the physical distribution of the causal loci in the genome been examined. Using simulated data, we show that these characteristics have major influence on the inferences of the genetic architecture of traits we can infer using chromosome partitioning analyses. In particular, small variation in chromosome size, small sample size, low heritability, a skewed effect size distribution and clustering of loci can lead to a loss of power and consequently altered inference from chromosome partitioning analyses. Future studies employing this approach need to consider and derive an appropriate null model for their study system, taking these parameters into consideration. Our simulation results can provide some guidelines on these matters, but further studies examining a broader parameter space are needed.