The large supermaxi yachts duelled for the lead in light 15-18 knot southerly winds on Sydney Harbour in front of a large spectator fleet before entering open ocean in the 628 nautical-mile (1,163km) race to Hobart.
With several changes in the weather forecast in the lead up to the race, skippers predicted an especially challenging and unpredictable run to the Tasmanian capital.
The supermaxis, including defending champion Wild Oats XI and its local challenger Perpetual Loyal, are expected to sail up the mouth of the Derwent River sometime on Saturday.
The remainder of the fleet are forecast to face winds of 40-60 knots and waves of up to 12 metres early on Sunday just as they enter the notoriously volatile Bass Strait.
A repeat of the major storm that sank five yachts and killed six sailors in 1998 is unlikely, however.
The international competition has been boosted by 12 boats from the Clipper Round the World Race, which for the first time is including the iconic ocean classic often referred to simply as "The Hobart", as part of its 40,000 nautical mile, 11-month race.
The Sydney to Hobart is a sporting staple of the festive season in Australia with the race start being held during the lunch break of the first day of the fourth Ashes test match at the Melbourne Cricket Ground.
Wild Oats XI holds the race record of one day, 18 hours, 23 minutes and 12 seconds set last year and is attempting to win the race for a record-equalling seventh time.