Contador, the 32-year-old from Tinkoff-Saxo, completed the final 178km processional stage from Turin safely in the main peloton to secure the eighth Grand Tour win of his illustrious career.
The Spaniard survived a dislocated shoulder, numerous spills and multiple attacks from rival team Astana over three brutal weeks in Italy to win the race by 1min 53sec over Italian Fabio Aru. Another Astana rider, Mikel Landa of Spain, completed the podium at 3:05.
Victory in the race's 21st and final stage went to Belgian track specialist Keisse of Etixx-QuickStep who outfoxed fellow escapee Luke Durbridge (Orica-GreenEdge) in the circuit race finale in Milan.
Blazin' Saddles: The story of the 2016 Giro d'Italia
Keisse and Australia's Durbridge benefited from a curious spate of punctures in the peloton to hold onto their advantage after attacking on the second of seven 5.4km laps in Milan.
Switzerland's Roger Kluge (IAM Cycling) led the pack over the line nine seconds in arrears ahead of Russia's Alexander Porzev (Katusha) and Italy's Giacomo Nizzolo (Trek Factory Racing), who secured the red points jersey despite – like Contador – failing to win a stage during the race.
BREAKAWAY UPSET: When Keisse and Durbridge edged clear of the pack with 30km remaining, few would have given the pair much chance of contesting the victory in half an hour’s time.
But when many of the sprinters’ teams were victims of a raft of punctures the leading duo saw their gap balloon to one minute with 12km remaining.
The likes of Luka Mezgec (Giant Alpecin), Bernie Eisel (Team Sky), Philippe Gilbert (BMC) and Heinrich Haussler (IAM Cycling) were among scores of riders needing mechanical assistance – with speculation pointing the finger at a cobbled section with tramlines 150m ahead of the finish line as well as the possibility of tacks on the road.
Despite the best efforts of the Trek Factory Racing team of Nizzolo and Sacha Modolo’s Lampre-Merida train – whose opposing riders came to blows earlier in the stage ahead of the second intermediate sprint that all but secured Nizzolo the red jersey – Keisse and Durbridge held a 38-second gap with four kilometres remaining.
Having collaborated well together to ensure their lead withstood the chase, the pair could start to play for the stage win as the finish line beckoned. Keisse, 32, used his experience and track skills in the final, refusing to pull and sitting on the back wheel of his younger rival.
And when Keisse responded to Durbridge’s dig on the cobbled section with his own decisive surge, it was the Australian who was first to congratulate him over the line in a sporting gesture worthy of the race’s final day.
Victory in Milan was Keisse’s second of the season and the biggest of his road racing career.
"We had a plan for me or Saba [Fabio Sabatini] to attack the sprinters on the final bend but I saw an opportunity and I went with Luke Durbridge as my partner in crime,” said Keisse.
"I pulled for the last time with 1.5km to go when I saw that we still had 30 seconds, so I put the pressure on Luke’s shoulders and refused to come through again.
"I’m so happy for the win and for the team – it’s our first of the race and we’re used to winning much more in the Giro.”
CONTADOR HOLDS ON: A split in the peloton meant the Spaniard conceded nine more seconds to his big rival Aru on the last day of the race – but it was not enough to prise the pink jersey from his shoulders.
Aru finished the race strongly with back-to-back stage wins in the Alps, the second of which saw Contador lose more than two minutes after being distanced on the dirt tracks of the Colle delle Finestre.
But Contador had the luxury of being able to put a cap on his efforts, knowing that the cushion he had built up during the second week of the race – most notably during the sodden individual time trial in the Prosecco region of north-east Italy – was large enough for him to secure the second Giro crown of his career.
If the history books say this was his second win, Contador still sees it as a third victory – the Spaniard provocatively holding up three fingers to the cameras as he defiantly clinged on to the 2011 overall win that was overturned in the wake of his retroactive two-year Clenbuterol ban.
Contador’s second official Giro title was won in the same manner as his first in 2008 in that he failed to win a stage during the 21 days of action.
In stark contrast, the two men who stood alongside Contador on the final podium in Milan – Astana’s Aru and Landa – both won two mountain stages each, adding to their dominating team’s earlier scalp through veteran Italian Paolo Tiralongo.
If five stage wins underlined Astana’s strength in depth, team management will be hoping Vincenzo Nibali – the reigning Tour de France champion – will be more successful in keeping Contador at bay in July when the Spaniard bids to secure the second half of his tilt at a rare Giro-Tour double.
Costa Rica’s Andre Amador (Movistar) and Canadian 2012 winner Ryder Hesjedal (Cannondale-Garmin) completed the top five in Milan, while Aru walked away with the white jersey youth standings by an advantage of almost two hours on fellow Italian Davide Formolo, a team-mate of Hesjedal who impressed in the race’s opening week with a strong stage four win in La Spezia.
Nizzolo secured the red jersey with a 33-point advantage over double stage winner Gilbert, while Italian Giovanni Visconti’s heroics in stage 19 were enough to secure the Movistar man the blue mountains classification.
Given their domination it will come as no surprise that Astana won the team standings by over 43 minutes on Gilbert’s BMC team.
But the battle that matters most – for the fabled maglia rosa – was won by a man whose further participation in the race looked unlikely after a crash on the final straight in Castiglione delle Pescaia in stage six saw him dislocate his shoulder.
Contador rode through the pain – and even withstood the unprecedented experience of losing the race lead in a Grand Tour for the first time in his career after another crash held him up on the approach to Jesolo in stage 13.
But that dominant ride in the 60km time trial was the pendulum swing. Aru lost the pink jersey after just one day before a series of strong performances in the Alps saw Contador pull out what became an unassailable advantage.
Focus now shifts to the Tour de France which starts in the Dutch city of Utrecht on Saturday 4 July. Contador will enter the race as one of the main favourites but will find the competition far sterner from the likes of Nibali, Briain’s Chris Froome (Team Sky) and Colombian Nairo Quintana (Movistar).
One thing's for certain: if Contador is to become the first rider since the late Marco Pantani in 1998 to win a Giro-Tour double he will need a far stronger team. For all his individual brilliance over the three weeks in Italy, Contador was frequently left isolated while Astana so often had power in numbers.
That Contador could win the 2015 Giro d'Italia pretty much off his own bat goes to show just why he is without a doubt the best stage racer of his generation.