Tilapiines are one of the most widely farmed fish species and currently being cultured in >100 countries in the World. Over the last few years, large-scale mortalities have been reported in tilapia due to infection with orthomyxo-like virus i.e. Tilapia Lake Virus (TiLV) which is considered as a threat to global tilapia industry. In the present study, we report outbreaks of TiLV disease in farmed tilapia in two states, West Bengal and Kerala from India. Diseased fish exhibited lethargy, inappetance and skin erosions with >85% mortality. TiLV infection was confirmed on the basis of PCR amplification and sequencing of segment 3 of TiLV, histopathology, infection of fish cell line and bioassay. CLUSTALW alignment of the partial sequences of segment 3 of the TiLV revealed that North 24 Parganas (MF502419) and South 24 Parganas (MF582636) of West Bengal, India showed 97.2% and Ernakulam, Kerala, India (MF574205) showed 96.4% similarity with TiLV from Israel (KJ605629.1). In histopathology, typical syncytial giant cells in liver and congestion of the blood vessels along with haemorrhages in sections of brain tissue were observed. The filtered tissue homogenate prepared from liver and brain of affected tilapia produced cytopathic effects in CFF cell line derived from Pristolepis fasciatus. The disease was successfully reproduced in naive tilapia following injection of culture supernatant from infected cell line and TiLV was successfully reisolated from experimentally infected tilapia. This is the first report of TiLV from India and adds to the reports of TiLV outbreaks in five countries across three continents. •Mortalities were observed in farmed tilapia from West Bengal and Kerala, India.•Samples were positive for tilapia lake virus(TiLV) in RT PCR amplification.•NCBI-BLAST of the PCR amplicons showed maximum similarity with TiLV from Israel.•Typical syncytial giant cells were observed in sections of liver.•Filtered tissue homogenate from liver and brain of affected tilapia produced CPE in CFF cell line.