Cryptosporidiosis is a significant public health concern in low-income countries, causing diarrhea-related morbidity and mortality. Cryptosporidium infection also affects livestock, leading to economic losses, with farm animals potentially serving as reservoirs for human transmission via contaminated food and water. Despite its importance, the epidemiology of cryptosporidiosis in Eastern Ethiopia remains poorly studied. A health facility and community based cross-sectional study was conducted between November 2022 and November 2023 in Dire Dawa Administration and Shinile, Eastern Ethiopia by including 756 children under five years of age with diarrhea, 184 community children, and 628 young livestock. Sociodemographic and other relevant variables were collected using a structured questionnaire and checklist. Fresh fecal specimens from children and livestock were collected, and initial stained by LED fluorescence microscopy, while remaining stool samples were stored at −20 °C for ELISA and molecular analyses. Stool samples tested positive by LED fluorescence microscopy and/or ELISA were processed by PCR targeting the small subunit ribosomal ribonucleic acid and glycoprotein 60 loci. Poisson regression with robust variance and Firth logistic regression were used to assess factors associated with Cryptosporidium infection. The prevalence of Cryptosporidium infection, as detected by LED-AP microscopy, was 15.2% among diarrheic children, 6.5% among community children, and 4.3% among young livestock. In children, C. hominis (64%) and C. parvum (36%) were identified, with gp60 subtype families Ia, Ib, and Id for C. hominis and IIe and IIc for C. parvum; the predominant subtypes were C. hominis IdA15 and C. parvum IIeA10G1. Among livestock, C. ubiquitum, C. xiaoi (subtype XXIIIg), and C. ryanae were detected. In children, Cryptosporidium infection was significantly associated with season, caregiver educational status, contact with diarrheic individuals, exclusive breastfeeding, handwashing after toileting, and use of toilet paper after defecation. In livestock, herd/flock size, source of drinking water for animal and animal caregiver age were significantly associated with Cryptosporidium infection.