The reserve is located between latitude 8° 25' and 8° 53' N and longitude 77° 10' and 77° 35' E, about 45 km west of Tirunelveli Town, and forms the catchment area for 14 rivers and streams. Among these rivers and streams, the Ganga, Tambraparani, Ramanadi, Karayar, Servalar, Manimuthar, Pachayar, Kodaiyar, Gadananathi River, and Kallar form the backbone of the irrigation network and drinking water for the people of Tirunelveli, Turicorin and part of Kanyakumari District. Seven major dams—Karaiyar, Lower Dam, Servalar, Manimuthar, Ramanadi, Gadananathi River and Kodaiyar—owe their existence to these rivers.
The reserve spans a range of 40 to 1,800 m in elevation. Agasthiyamalai (1681 m.) is in the core zone of the reserve.
KMTR is approachable by Rail and Road from Tirunelveli (it is well connected to all parts of the State and Country).
The nearest Air Ports are Tuticorin, Madurai in Tamil Nadu and Tiruvandram in Kerala.
The Road distances (Kms.) from Railway Station and Airport to the Tiger Reserve are as follows:
- Madurai Airport to Mundanthurai : 215 km
- Tuticorin Airport to Mundanthurai : 100 km
- Madurai Airport to Kalakad : 210 km
- Tuticorin Airport to Kalakad : 80 km
- Madurai Airport to Tirunelveli : 167 km
- Tuticorin Airport to Tirunelveli : 40 km
- Thiruvandram Airport to Mundanthurai : 200 km
- Thiruvandram Airport to Kalakad : 140 km
- Tirunelveli Railway Station to Mundanthurai : 50 km
- Tirunelveli Railway Station to Kalakad : 45 km