The ‘Shark of Messina’ successfully defended the race as Tony Martin (Omega Pharma–QuickStep) won the stage.
Astana rider Nibali claimed a 34 second lead on GC from Britain's Froome after finishing in the leading three-man group in Monday's crucial stage.
The Team Sky rider posted a time of 10 minutes 40 seconds - good enough for sixth on the stage - and gained 11 seconds on Nibali but the Sicilian still won the race overall by 23 seconds.
Alberto Contador (Saxo Bank-Tinkoff Bank) completed the podium, his time good enough for 15th and putting him just two seconds ahead of time-trial specialist Michal Kwiatkowski (Omega Pharma-Quick-Step), who could only manage eighth on the 9.2km course on wide avenues beside the Adriatic Sea.
Nibali said: "There were one or two difficult corners with the rain and I preferred to take no risks.
"It was a great Tirreno-Adiratico, and it gives me great personal satisfaction to win against riders of the quality of Contador and Froome, like in the great three-week races."
Joaquim Rodríguez (Katusha) was a contender for GC but finished in inauspicious circumstances with 33rd to miss out on fourth overall by one second.
World time trial champion Martin set the benchmark time of 10:25 which was six seconds faster than Adriano Malori (Lampre-Merida) with Andrey Amador Bakkazakova (Movistar) at 10 seconds a surprise third-place finisher.
"I was looking for this day because the mountains weren't for me," said Martin in reference to the previous three stages, in particular stages four and five.
RadioShack Leopard Trek's Fabian Cancellara, who won the finishing time trial at the last two editions of the race, was part of a 160km breakaway on Monday yet managed a time of 10:37 to finish fourth on the ITT ahead of Jonathan Castroviejo Nicolas (Movistar).
The early riders were at a disadvantage as rain fell in the morning and early afternoon, stopping before the start - and the roads dried out as the stage continued.
That favoured the GC hopefuls, going last, and meant a fairly level playing field among them.
Tronto has hosted the final stage finish of every Tirreno-Adriatico since the race’s second edition in 1967.