The Spaniard, defending his Copa Claro title, had to fight from a set down against the former world number three but came through the test to make it two wins from two since getting his clay court season up and running in Argentina.
Having despatched wild card Agustin Velotti in the first round, Ferrer turned his attentions to Nalbandian, who had reached the final on the red dirt in Sao Paulo earlier this month.
Nalbandian posed an altogether different threat to Velotti though, and the Argentine proved it early on in an excellent first set during which he won 81 per cent of his first service points and broke Ferrer's serve twice.
Ferrer is not ranked fourth in the world at the moment for nothing though, and in typical fashion the top seed dug in and fought back to take the second set, bringing up two break points and crucially taking one of them.
Having levelled the match, the final set became a formality for Ferrer, who raced through it without loss of a single game to set up a last-eight meeting with Fabio Fognini, who beat local player Marco Trungelliti.
"David (Nalbandian) is a player who dominates from the start," Ferrer said. "I knew to beat him it would have to be a long match _ beating him physically."
Earlier in the day, second seed and last year's losing finalist Nicolas Almagro also moved into the quarter-finals with a 7-6(5) 6-2 win over Andrey Kuznetsov of Russia.
Almagro, bidding to reach the final in Argentina's capital for a third time, was not at his best and had to save seven break points on his way to wrapping up the win in an hour and 23 minutes.
"It was not a very good match for me," Almagro said. "The important thing is being in the quarter-finals again."
The world number 11 now faces qualifier Federico Delbonis, who defeated Albert Montanes 6-1 6-4.
Stanislas Wawrinka, the next highest seed behind Ferrer and Almagro, matched his rivals with a 6-1 6-4 win over Daniel Gimeno-Traver of Spain.
The Swiss now meets another Spaniard Albert Ramos, who booked his place in the quarters with a 6-3 7-6(3) win over Leonardo Mayer of Argentina.
Juan Martin Del Potro came from a set down to book his place in the Marseille Open third round with a 3-6 7-6(4) 7-5 win against Michael Llodra.
Cheered on by a home crowd, Llodra took the opening set against the second-seeded Del Potro, and was tantalisingly close to victory when the second went to a tie break.
But the big-serving Argentine held his nerve, before wrapping up a tight final set 7-5.
Gilles Simon gave the French fans something to cheer when he dispatched Spain's Roberto Bautista 6-3 6-1.
In Memphis, top-seeded Marin Cilic saved three match points to narrowly avoid becoming the latest upset at the US tournament.
Cilic avoided the same fate that befell second seed Milos Raonic on Wednesday despite trailing 6-4 and 7-6 in the third set tiebreak against Igor Sijsling, who double faulted on his third match point to allow Cilic to steal the tie-break 9-7 and set up a quarter-final against Japan's Kei Nishikori. World number 22 Nishikori beat Donald Young of the US 6-3 6-3.
The Croat's recovery ensured he did not become the second seeded player in the men's draw to lose on Thursday after fourth seed Sam Querrey lost momentum in the second set of his match and was beaten 3-6 6-4 7-5 by Australia's Marinko Matosevic.
Buenos Aires Open results:
3-Stanislas Wawrinka (Switzerland) beat Daniel Gimeno-Traver (Spain) 6-1 6-4
1-David Ferrer (Spain) beat David Nalbandian (Argentina) 2-6 6-4 6-0
8-Albert Ramos (Spain) beat Leonardo Mayer (Argentina) 6-3 7-6(3)
Tommy Robredo (Spain) beat Diego Schwartzman (Argentina) 6-3 6-1
6-Fabio Fognini (Italy) beat Marco Trungelliti (Argentina) 7-5 6-2
2-Nicolas Almagro (Spain) beat Andrey Kuznetsov (Russia) 7-6(5) 6-2
Federico Delbonis (Argentina) beat Albert Montanes (Spain) 6-1 6-4
Julian Reister (Germany) beat Aljaz Bedene (Slovenia) 6-1 1-6 6-2
Marseille Open results:
7-Jerzy Janowicz (Poland) beat Julien Benneteau (France) 7-6(0) 6-3
2-Juan Martin Del Potro (Argentina) beat Michael Llodra (France) 3-6 7-6(4) 7-5
6-Gilles Simon (France) beat Roberto Bautista (Spain) 6-3 6-1
Dmitry Tursunov (Russia) beat 4-Janko Tipsarevic (Serbia) 7-6(4) 6-2
Memphis International results:
Feliciano Lopez (Spain) beat 6-Tommy Haas (Germany) WO
Jack Sock (U.S.) beat James Blake (U.S.) 7-5 6-4
Marinko Matosevic (Australia) beat 4-Sam Querrey (U.S.) 3-6 6-4 7-5
5-Kei Nishikori (Japan) beat Donald Young (U.S.) 6-3 6-3
1-Marin Cilic (Croatia) beat Igor Sijsling (Netherlands) 7-6(2) 3-6 7-6(7)
7-Alexandr Dolgopolov (Ukraine) beat Rhyne Williams (U.S.) 6-4 4-6 6-4
Denis Istomin (Uzbekistan) beat Lleyton Hewitt (Australia) 6-1 6-2
Michael Russell (U.S.) beat Lukasz Kubot (Poland) 6-2 6-4