The normally reliable keeper let a speculative 40-yard drive from on-loan midfielder Adnan Ahmed slip through his fingers in the 85th minute.
His grotesque gaffe heaped yet more pressure on under-fire boss Keith Alexander who has now seen his Macclesfield side take only one point from the last 18.
Worse was to follow for the Cheshire side as Valiants sub Louis Dodds sealed the result with a fierce half-volley deep in to stoppage time.
It was sweet revenge for the Valiants who had suffered two defeats before Christmas to their country cousins leaving their fans fuming and desperate for a payback.
Macclesfield had had the better chances in the second half with midfield man Jordan Hadfield stinging the hands of keeper Joe Anyon in the seventh minute with a powerful 20-yard shot.
Then, in the 16th minute, Danny Thomas produced a glancing header that had Anyon diving full length to claw the ball wide.
Macc again went close four minutes later when right-back Izak Reid moved in off the right flank only to blast wide with the far corner of the goal gaping.
Vale started producing gaps in the closing stages and in the 74th minute Marc Richards sent a powerful volley from a narrow angle inches past the far post.
Richards again went close moments later when he got on to the end of a cross from Kevin Gall only to fire over the bar. Neither side looked like scoring before Brain sealed the outcome with his pantomime howler.