Introduction Leishmaniasis is a neglected vector borne disease, which constitutes a major public health concern in several tropical and subtropical countries. An estimated 4500 to 4000 new cases of visceral leishmaniasis (VL) occur per year and over 3.2 million people are at risk of infection in the country. In Humera, VL epidemics are associated with migration of workers from nonendemic highlands into the visceral leishmaniasis endemic extensive farmlands. Therefore, the objective of this study is to estimate the incidence and the risk factors of leishmaniasis in Humera, Western Tigray. Methods A retrospective study was conducted using the hospital admission database on all patients admitted who have been suspected of having leishmaniasis infection and tested for rK39-based immune chromatographic test (ICT) at Kahsay Abera Hospital in Humera town from January 2012 to December 2017. Potential risk factors for leishmaniasis infection in human were collected from the hospital, which included categorical variables: age, sex, origin of place, clinical forms of leishmaniasis, mortality rates, and the occurrence of infections according to format of hospital. Results A total of 26511 hospital discharged patients with diagnosis of leishmaniasis were identified, out of which 2232 (8.42%) human leishmaniasis cases were registered and of them 71 were dead from January 2012 to December 2017. Mortality rates of leishmaniasis were 18 (3.3%) in 2012, 16 (3.1%) in 2013, 15 (2.4%) in 2014, 8 (3.3%) in 2015, 9 (4.1%) in 2016, and 5 (5.4%) in 2017. Univariate analysis of the infection rate of leishmaniasis was based on the potential risk factors and found higher male infection rates than female (P <0.05) in all the study years. Origin of place was also significantly associated (P< 0.05) where labor migrants from highland to agricultural fields had higher infection rates than those who permanently lived in and around Humera. Trends in season of occurrence revealed that weeding and harvesting time (July–December) had higher incidence of leishmaniasis than dry time (January–June). Conclusion Male labor migrants from the highlands older than 15 years of age were at the highest risks of leishmaniasis during weeding and harvest season. Therefore, awareness creation on the risks of sleeping outdoors and the impact of using of bed nets is imperative especially for labor migrants during weeding and harvesting season.