Malaria is a significant public health concern that caused 409,000 deaths in 2019. During malaria, Th1 cells produce pro-inflammatory cytokines to promote parasite clearance. However, IL-10-producing Th1 (Tr1) cells develop to protect tissues, but also suppress Th1 cell-mediated immune responses, contributing to the persistence of infection. To try and better understand the development of Th1 and Tr1 cells during malaria, we performed an RNAseq on Th1 and Tr1 cells from human volunteers participating in controlled human malaria infection (CHMI) studies with Plasmodium falciparum and identified TMEM173 (coding STING) to be more up-regulated in Tr1 cells than Th1 cells. We then employed CRISPR-Cas9 technology to knock down TMEM173 transcription in human CD4+ T cells. We found that STING activation was critical for the development of Tr1 cells, promoting the expression of interferon (IFN) β1 and IL-10, as well as co-inhibitory receptors (CIRs). In contrast, activation of STING in CD4+ T cells suppressed the generation of Th1 cells in vivo. Moreover, we confirmed that STING-mediated development of Tr1 cells required type I IFN signalling, but also discovered that the inhibition of Th1 cell development occurred through a STING-intrinsic but type I IFN-independent mechanism. Importantly, we found that malaria parasites stimulated the expression of IL-10 by CD4+ T cells and increased the sensitivity of Tr1 cells to STING activation. Finally, we found that the JAK1/2 inhibitor ruxolitinib inhibited the STING-dependent generation of Tr1 cells, identifying it as a potential host-directed therapy for improving anti-parasitic immunity during malaria. Together, this data identifies a key CD4+ T cell innate signalling pathway that drives anti-inflammatory immune responses during malaria, as well as a drug to modulate this response.