St Patrick's High School in Keady received the award at an event in London on Friday night.
The judges said the "innovative work and move away from banding, the amazing results achieved and rate of acceleration" made St Patrick's stand out.
They also praised the school's work in the community.
In 2011, only 51% of GCSE pupils at St Patrick's were achieving five A*-Cs including English and maths.
By 2014 it had become the highest-performing non-selective school in Northern Ireland, with 80% of pupils achieving those results and 93% leaving with five GCSEs.
TES said St Patrick's had abandoned streaming and banding, focused on teaching and learning, motivating and engaging boys, and assessment for Learning.
It said it also built stronger links with its partner primary schools and a learning resource centre now assists students who are struggling.
"But it's not all about the academic side: St Patrick's is prominent in the local community, sending food hampers to those in need at Christmas and organising regular visits to the elderly," it said.
"As the school's entry to the TES Schools Awards pointed out, the emphasis is on education in its 'fullest sense'."
The TES (formerly Times Education Supplement) school awards are in their seventh year.
Winners in 17 categories were announced on Friday.
A County Armagh school has been voted best secondary school in the UK in the 2015 TES school awards.