Circular RNAs (circRNAs) are a new frontier in the diverse and ever-growing world of RNA. Recent expression profiling studies show that circRNAs are expressed in a regulated manner across eukaryotes but we currently lack a systematic understanding of the cellular phenotypes and signalling pathways that are regulated by circRNAs. A major gap in understanding circRNAs functions is the ability to define the pathways that are regulated by circRNAs in a high-throughput and unbiased manner. Here, we generated a pooled shRNA library targeting the unique back-splice junction of 3,354 circRNAs that are expressed at low to high levels in humans. We used this library to perform loss of function proliferation screens in a panel of 18 cancer cell lines from four different tissue types (colorectal, pancreas, skin and central nervous system) that harbour mutations leading to constitutive activation of defined cellular signalling cascades (MAPK and WNT/beta-catenin). Using this data set we performed a two-class comparison analysis of circRNA dependency scores in pathway active versus inactive cell contexts and this has revealed certain pathway-specific and cell-essential functional circRNAs. We validated these observations with a secondary screen and then we performed mechanistic studies and uncovered the cell essential roles of circRERE in regulating the iron-dependent form of cell death, ferroptosis, and circHUWE1 in regulating apoptosis. Furthermore, we characterised the functional roles of pathway-specific circRNA, circSMAD2, a novel regulator of the WNT/beta-catenin pathway and of circMTO1, a regulator of MAPK signalling in a PTEN dependent manner. Our work adds a circular dimension to this and sheds light on how core mammalian developmental molecular pathways that can drive cancer are regulated by circRNAs and provides a catalogue of circRNAs with a measurable function in human cells.