Lower league Salisbury ended Wrexham's three-month unbeaten run to knock Dean Saunders' men out of the FA Trophy.
Jake Reid was the Salisbury match-winner when he sent Wrexham keeper Chris Maxwell the wrong way from the penalty spot in the 26th minute.
Wrexham boss Saunders rotated his squad but they dominated the first half and failed to create a chance except when Adrian Cieslewicz fired over the bar.
But the Zamaretto Premier Division side held on to move into the third round.
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