Allogeneic hematopoietic stem cell transplant (alloHSCT) can be a life-saving treatment for patients with hematological disorders but far too often carries the feared complication of graft-versus-host disease (GVHD). The first-line treatment of GVHD is typically corticosteroids, but steroid-refractory chronic GVHD (cGVHD) has led to the Food and Drug Administration (FDA) approval of ruxolitinib (Jakafi), ibrutinib (Imbruvica), and belumosudil (Rezurock).Patient 1 was a four-year-old female diagnosed with natural killer (NK) cell dysfunction who underwent alloHSCT with cells from a 9/10 National Marrow Donor Program (NMDP) donor and subsequently developed chronic GVHD (cGVHD) of the skin and gut. This cGVHD was refractory to steroids and ibrutinib but improved with the administration of concomitant ibrutinib and ruxolitinib. Patient 2 was a one-year-old male with sickle cell anemia. The patient was transplanted under a haploidentical protocol from the mother but developed bronchiolitis obliterans organizing pneumonia (BOOP) and pathology-confirmed GVHD. This cGVHD was steroid-refractory and resolved with the administration of concomitant ibrutinib and ruxolitinib. To our knowledge, this is the first reported use of concomitant ruxolitinib and ibrutinib in pediatric patients. The combination was well tolerated with no significant adverse events. Neither patient had to discontinue these drugs. We propose a further investigation into this dual therapy in cGVHD either compared to steroids or as a second-line option.