Using a clinical isolate (Af293), a small portion of the A. fumigatus genome (922kb centered round the niaD locus) was successfully sequenced and annotated in 2004 by a UK-based team (The University of Manchester and The Wellcome Trust Sanger Institute). This pilot project led to an international effort to analyse the full genome.

Seven centres collaborated to sequence and generate first-pass annotation of this genome: The Wellcome Trust Sanger Institute, The J. Craig Venter Institute (JCVI formerly known as TIGR), The University of Manchester, The Pasteur Institute, The University of Salamanca, Complutense University, and Centro de Investigaciones Biológicas. Many other experts then joined this group to manually refine the annotation and to perform analysis between A. fumigatus, A. nidulans and A. oryzae. The resultant genome was released in December 2005.

This genome was sequenced by the whole-genome random shotgun method, giving 10.5x coverage, and was refined by optical mapping. Closure was obtained by directed sequencing and manual editing. First-pass annotation was carried out by the JCVI pipeline 'Eurkaryotic Genome Control'. The task of managing and directing further annotation of this genome was undertaken by The University of Manchester via JCVI's annotation system 'Manatee'.