The pub chain has owned the Grade II-listed former girls' school on Richmond Road for several years - but has been thwarted in its previous attempts to turn the building into a bar following opposition from residents living nearby.
If approved, the development would have 52 bedrooms with 28 parking spaces and create 50 new jobs.
Planning permission for change of use into a pub was granted into 2016, but the project failed when Wetherspoons were denied an alcohol licence. Both decisions were made during appeals. The property falls within Headingley's Cumulative Impact Zone, which restricts the number of establishments selling alcohol within a defined area unless certain terms are met to prevent crime and disorder.
The company is still committed to restoring the 'architecturally significant' building and will open a small bar area as part of the hotel. The current site does not have capacity for 50 guest rooms and so a separate application has been submitted to extend the building to ensure it is economically viable.
Wetherspoons already operates hotels around the UK.
The building has been empty since 2010, when it was vacated by the now-defunct Leeds Girls' High School, who used it as a concert hall and theatre. Community organisation Leeds Music Hub expressed interest in turning the site into a music centre.A decision from Leeds City Council on the application is currently pending.