Background: ESBL producing E. coli is among the most important strains of public health concern due to their resistance to antibiotics. In order to reduce infection and deliver adequate treatment of cattle and humans, it is important to know the prevalence and drug resistance patterns of ESBL producing E. coli in both humans and Cattle and the transmission route between them. The objective of this study was to determine the prevalence and drug resistance patterns of ESBL producing E. coli isolated in Cattle in Moshi urban and humans at KCMC Hospital. Methods: A cross sectional study was used to enroll 200 cattle fecal specimens in Moshi urban and 215 urine and stool specimens from human at the KCMC Clinical laboratory. Bacterial isolation, identification and antimicrobial susceptibility testing were performed based on the standard operating procedures (SOPs). Results: A total of 415 specimens was used, of which 200 Cattle fecal specimens, 108 human urine and 107 human stool specimens. Among the isolate, ESBL producers were 32/200 (16%) in cattle fecal and 89/215 (41.4%) human specimens. More than 63% of isolates were resistant to all of the tested antimicrobials. Conclusion: ESBL producing E. coli is common among patients at KCMC hospital as well as cattle in Moshi urban, Tanzania. These findings suggest that, the nation should provide health education on the effect of misuse of antimicrobial agents without prescription from professionals in both cattle and human. Keywords: Extended, spectrum, beta, lactamase, Drug, resistance, patterns, Tanzania