Sinclair kept his cool when sent clear to finish in fine style and give Gary Simpson's Silkmen a surprise 17th-minute lead and struck again in similar circumstances just before the hour mark.
The two sides have experienced vastly different fortunes since last playing each other in 2004 when they were both in the old third division, but there was little between them throughout the contest and the visitors bravely defended their two-goal lead in the closing stages.
Hull made seven changes from the side beaten last Friday night by Blackpool in their opening league game, with defender Danny East, goalkeeper Adriano Basso and new signing Martin Pusic making their debuts and Andy Dawson, James Harper, Jamie Devitt and Jay Simpson all coming back into the side.
Macclesfield defender Carl Tremarco, striker Emile Sinclair and midfielder Lewis Chalmers were recalled by the visitors.
Hull striker Matty Fryatt forced a good save from Macclesfield goalkeeper Jose Veiga in the 12th minute, but the visitors stunned most in the KC Stadium when Sinclair tucked home Tremarco's raking pass into the penalty area to score the opening goal five minutes later.
Fryatt and East saw efforts fly wide and over the crossbar respectively and Harper's angled shot from inside the area was blocked as Hull looked to restore parity before the break.
Macclesfield doubled their lead in the 59th minute. Jonathan Bateson played a long ball over the top and Sinclair again sprang the Tigers' offside trap to race clear and steer a low shot into the bottom corner.
Macclesfield left only Sinclair up front soon after, but soaked up everything Hull could muster and although Jack Hobbs, McKenna, Jamie Devitt and Nick Barmby all fired in shots that were blocked or just off target, the Tigers could not make the breakthrough.