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Club captain Grabban came off the bench and scored with just seven minutes of the 90 left to play as the woeful Gunners fell at a rocking City Ground once more.
Arsenal’s only previous defeat at this stage of the famous old competition in the last 26 years also came at this venue under Arsene Wenger back in 2018.
Arsenal made seven changes from their last-gasp Premier League defeat by leaders Manchester City on New Year’s Day, with highly-rated youngster Charlie Patino handed his full senior debut amid a shortage of midfielders.
The visitors also wore a one-off all-white kit as part of an initiative with Adidas to combat knife crime and youth violence in London.
Forest boss Steve Cooper, meanwhile, handed debuts to new signings Steve Cook and Keinan Davis as part of a triple change following back-to-back defeats in the Championship.
The first half was a truly drab affair between two sides that each saw their last match postponed due to Covid-19 issues, with Arsenal notably sloppy in possession and static in their movement, while Forest’s final pass was repeatedly rushed when they broke forward.
The lack of VAR at the City Ground was a big relief for Joe Worrall, whose blatant shirt pull on Ben White as the two defenders jostled for position at an Arsenal corner would surely have otherwise been given as a penalty.
The most notable moment of a sleepy first half was Arsenal boss Mikel Arteta deciding to hook the disappointing Nuno Tavares after just half an hour following a wholly unconvincing display.
The Portuguese full-back was visibly unhappy with the decision as he made way for Kieran Tierney, tossing his gloves to the floor in frustration.
Forest - who boasted the best player on the pitch in full-back Djed Spence - started the second half in lively fashion and a lung-busting run from Brennan Johnson set up a chance for Watford loanee Philip Zinckernagel, whose cushioned volley was pushed wide by Bernd Leno.
Eddie Nketiah was then teed up by a great cross from Bukayo Saka, but he got his header all wrong before Leno was forced into another flying save from James Garner’s free-kick.
Jack Colback’s strong appeals for a penalty were then waved away after a little push from Saka.
Forest were clearly the better side and the deadlock was finally broken seven minutes from time, with substitute Grabban - introduced in place of Aston Villa loanee Davis - sliding in to turn home Ryan Yates’ excellent early right-wing cross after Albert Sambi Lokonga had crucially given the ball away for Arsenal.