The Spanish champions announced on Friday that Vilanova, 44, was unable to continue because of the demands of his cancer treatment and the club said on Tuesday they had hired 50-year-old Argentine Martino, a former Newell's Old Boys coach in his native Rosario, on a two-year contract.
Barca's Argentina forward Lionel Messi is also from Rosario and the 26-year-old World Player of the Year, increasingly influential thanks to his phenomenal goalscoring record in recent years, reportedly had a hand in Martino's appointment.
The silver-haired former Newell's player is a self-confessed admirer of Barca's most successful coach, Pep Guardiola, who handed the reins to his friend Vilanova at the end of the 2011-12 season and is now at Bayern Munich.
Martino's football philosophy, rooted in ball possession and relying on players with outstanding technical ability, is considered a snug fit with Barca's playing style.
"My priority is possession," Martino said in an interview in May 2012, according to Barca's website (www.fcbarcelona.com).
"Attack, get a lot of players in the opposition half, take risks," he added.
Vilanova's debut season after succeeding Guardiola was a disappointment by Barca's high standards even though they wrested the La Liga title back from arch rivals Real Madrid with a record-equalling points haul.
Towards the end of the campaign, there was a sense some of the players had lost their focus because of Vilanova's illness.
He was away in New York having treatment for two months in February and March and although he was back on the bench for the end of the season Barca's Champions League campaign was brutally cut short by Bayern Munich.
The players seemed spent and barely put up a fight against the aggressive Bundesliga side in the two-legged semi-final and their 7-0 aggregate reverse was the club's worst in Europe by some distance.
In recent weeks as Real began to regroup for next season under new coach Carlo Ancelotti, Barca's preparations were again overshadowed by the issue of Vilanova's health.
Guardiola, the club's most successful coach, accused the Barca board of using Vilanova's illness to damage him and the issue dominated media coverage for several days.
When it became clear Vilanova could not continue, president Sandro Rosell and sporting director Andoni Zubizarreta knew they had to move rapidly to fill the gap with the new La Liga season less than a month away.
Luis Enrique, a former Barca player who has just taken charge at Celta Vigo, was said to be in the running but they opted instead for Martino, a relative unknown in Europe but who won plaudits for taking Paraguay to the last eight of the 2010 World Cup.
Martino's link to Messi will help him settle and win the confidence of the other players, while in new signing Neymar he has one of the hottest properties in the game.
With Real having reinforced their squad with a couple of astute purchases and apparently recovering quickly from the turbulence of the Jose Mourinho years, Barca will have to be at the top of their game if they are to defend their La Liga title.
It is the Champions League that counts, however, and one of Martino's first jobs will be to make sure Barca find the centre back they need to strengthen the defence that let them down badly at times last season.
When the action starts, maintaining Barca's entertaining, attacking style while making sure the players are not bullied out of a match like they were against Bayern is likely to be his main challenge.
"I think he will fit in with our model," Barca's Spain midfielder Andres Iniesta told Marca on Tuesday. "Whatever the club decides is best for Barca."
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