The duo are the front runners in the nine-nation South American group heading into the final straight of the qualifiers with their coaches looking to ensure there is a good balance of hard work to go with the immense skill.
Messi, who stated his World Cup goal once again in midweek, is at the fulcrum of everything that is good about a dynamic team coached by Alejandro Sabella in which midfielders Javier Mascherano, Fernando Gago and Walter Montillo also shone.
Fans chanted favourite World Cup victory songs as Argentina displayed their attacking skills and also showed improvements in defence that reflect their work under Sabella.
Messi, who converted a penalty, is two goals short of the 34 Diego Maradona scored for Argentina, while Gonzalo Higuain's brace put him top of the South American scorers chart.
"We have a forward line that can be considered among the best in the world," Sabella told reporters.
"Venezuela are a tough team, very compact, who know what they want. What happened was that Argentina played very well, especially in the first half and were very superior."
Sabella said he asked for and got plenty of defensive help from his forwards and this will be important for Tuesday's match away to Bolivia in La Paz where visiting teams suffer the effects of the high altitude. Argentina lost 6-1 on their last visit.
Compatriot Jose Pekerman, whose second-placed Colombia side have notched up 19 goals to Argentina's 23, might have been talking about Argentina too when he referred to his Colombia team's strong form.
"It's hard to find teams with such skills and ball control although there are moments when you can't keep up the rhythm in these kinds of matches," he said after another win.
Colombia have a very realistic chance of ending a 16-year wait to play at the World Cup finals but Pekerman attempted to quash the hype.
"We have to keep calm and not get anxious. We don't think about the points we need to get to the World Cup, we'll carry on working," he said.
The other teams have their work cut out to keep pace although Ecuador, who had a bye on Friday, are in good shape in third place with the top four making it to the finals.
Ecuador crushed El Salvador 5-0 in a friendly on Friday before hosting Paraguay on Tuesday in Quito where they have picked up maximum points from five home matches.
Uruguay scraped back into the qualifying berths with a 1-1 draw at home to Paraguay but only because Venezuela lost. Luis Suarez scored his eighth goal in the qualifiers.
Coach Oscar Tabarez felt Uruguay had the better of the second half but conceded a late equaliser to a Paraguay side in bottom place and who look unlikely to reach the finals for the fifth time in a row.
"We know what we must do, lift our spirits and go in search of something we didn't get here," Tabarez added looking ahead to Tuesday's match away to Chile.
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