The autophagy pathway is critical for homeostasis, cell survival, cytoprotection, and regeneration. Evidence exists for transcriptional regulation of autophagy in the first few hours following stress or starvation. We hypothesize that composition, number and position of multiple TFBS are organized into distinctive clusters conserved among functionally related human autophagy gene promoter sequences. ATG3, ATG4A, ATG5, ATG4B, ATG7, MAP1LC3A, ATG9B, ATG10, ATG16l1, and ATG16l2 promoters were analyzed with pattern detection and pattern matching algorithms. Comparisons of composition, number, and position of predicted TFBS within conserved regions in aligned human autophagy gene promoters identified distinctive patterns of TFBS clusters. Each gene's upstream 2kb flanking sequence contained 129 to 600 TFBS of which 5-30 were conserved among subsets of autophagy genes. SP1, c/EBP alpha, and NF1 binding sites were most abundant. Distinctive clusters identified were found to be shared by several autophagy gene promoters. In some cases, multiple instances of a cluster were present in a single gene.Clusters differed among subsets of autophagy genes, suggesting differential regulation of autophagy pathway components. Functional annotation of candidate transcription factors allows us to predict regulatory pathways and physiological stimuli that affect autophagy gene transcription. This multi-algorithm a priori analysis approach together with experimental confirmation can inform gene expression and systems biology studies of autophagy.