Martin O'Neill was condemned to his first home defeat as Sunderland boss after Thierry Henry came off the bench to score a stoppage-time winner at the Stadium of Light.
James McClean gave the hosts the lead after Gunners defender Per Mertesacker injured himself trying to control the ball, firing past Wojciech Szczesny.
The German international was stretchered off, and his replacement Aaron Ramsey restored parity in the tie, smartly directing a shot past Simon Mignolet in the Black Cats' goal.
With the game all square and both teams settling for a share of the spoils, Henry came off the bench, and in his final league appearance for Arsenal before returning to the New York Red Bulls next week, volleyed the ball home to steal all three points.
The win lifts Arsenal up to fourth in the table, usurping Chelsea who fell to a 2-0 defeat at West Ham, putting Arsene Wenger's side back in contention of Champions League qualification.