The Robins were already a goal down when Aden Flint was handed his marching orders for a two-footed challenge and can have no complaints with either the sending-off or the defeat.
Macclesfield goalkeeper Lance Cronin made outstanding early saves from Raffa de Vita, Gary Roberts and Andy Williams.
Swindon paid for their wastefulness in the 63rd minute when Tony Diagne gave the Cheshire side the lead with a superb 35 yard free kick into the top corner.
Flint then saw red for his challenge on Amari Morgan-Smith.
Cronin then denied Simon Ferry from four yards before substitute Louis Thompson beat his own goalkeeper Wes Foderingham with a 30 yard back pass.