The group - which offers rooms for as little as £21 a night - has acquired the conditional lease on the former Scala Theatre in the city centre, which it is aiming to develop in to a 94-room hotel.
The site is expected to open in 2018 if planning permission is granted.
EasyHotel, the sister company to EasyJet, also confirmed this week that it has acquired a former Primark store in Sheffield with the aim of transforming it in to a budget hotel.
Guy Parsons, CEO at EasyHotel, said: "We are delighted to announce our second development project in line with our development strategy announced in September.
"Leeds, a northern powerhouse city, is already a major regional employment hub which will be further supplemented by the significant planned developments for the city, including the redevelopment of the former Tetley Brewery, Leeds Dock shopping area and HS2.”
EasyHotel is also set to open a 54-room hotel in Reading next year as part of a franchise deal with Splendid Hospitality Group.
The company operates 25 hotels in London, Liverpool, Glasgow, Manchester, Edinburgh and Birmingham and seven overseas countries including Germany and Dubai.