The Belgian started the day 11.9 seconds clear of Citroen's Sebastien Ogier, with Toyota's Ott Tanak a further 1.5 adrift, but both of those rivals suffered setbacks that scuppered their chances of winning.
Tanak retired with alternator problems on the afternoon loop of stages while six-times world rally champion Ogier hit a stone gatepost and lost almost a minute, the Frenchman dropping to fourth overall.
Northern Irishman Kris Meeke was in third place, one minute 03.2 seconds behind Neuville in his Toyota.
"We are in a very strong position but we still can’t take anything for granted. It has been an excellent day. We have enjoyed a good feeling in the car on all stages," Neuville said.
"We knew it would be tough to defend but we were able to maintain our lead and then saw that increase when Ott unfortunately retired.
"Knowing we had a margin, we were able to take it easier on the last stage, avoiding rocks and punctures."
Sunday's action takes in three stages, totalling 53.16km, near Villa Carlos Paz, to the west of the city of Cordoba in central Argentina.
The rally is the fifth round of the championship, with Neuville two points ahead of Ogier and Tanak a further three behind.
(Reporting by Alan Baldwin, editing by Ed Osmond)
