Due to its key role in dysregulated cellular signaling in cancer, AKT has been subject to intense drug discovery efforts leading to small molecule inhibitors investigated in clinical trials, notably breast cancer. To shed more light on how these drugs exert their therapeutic effects, we integrated chemoproteomic target affinity profiling using the kinobeads approach and phosphoproteomics for the five designated AKT inhibitors AZD5363, GSK2110183, GSK690693, Ipatasertib and MK-2206 in breast cancer cells. Kinobead analysis identified between four and 29 nanomolar targets for these compounds and revealed that AKT1 and AKT2 were the only common targets. Similarly, measuring the response of the phosphoproteome to the same inhibitors identified ~1,500 regulated phosphorylation sites among which 276 were regulated by all drugs. This analysis expanded the AKT signaling network by 119 phosphoproteins that may represent direct or indirect targets of AKT. Within this network, we found 29 regulated phosphorylation sites bearing the AKT substrate motif and recombinant kinase assays validated eight as novel AKT substrates. These included CEP170 and FAM83H, which suggest a direct regulatory function of AKT in mitosis and cytoskeleton organization. In addition, a specific phosphorylation pattern on ULK1, FIP200, ATG13 and VAPB was found to represent an active state of ULK1, leading to elevated autophagy in response to AKT inhibition. And last, secretome analysis of AKT inhibitor-treated cells identified STC2 as a putative blood-based drug response marker that may be tested in patients in the future.