Oscar Benitez netted either side of the interval to swing the game decisively in the host's favour after it had seen Jorge Pereyra Diaz's early opener cancelled out by Mauro Zarate.
Emiliano Papa reduced the deficit for the second-placed visitor 16 minutes from the end but it was not enough to prevent it slipping to its first loss of the season.
The result kept Velez two points behind Estudiantes, which visits Boca Juniors on Monday (AEDT).
Elsewhere, Racing Club goalkeeper Diego Sebastian Saja stepped up to score a 20th-minute penalty in his side's 3-1 loss at Arsenal Sarandi.
Saja's goal cancelled out Mariano Echeverria's opener, but further efforts from Ramiro Carrera and Julio Cesar Furch saw Arsenal well in control before half-time as it moved up to sixth in the table.
Finally, Juan Careaga's sixth-minute strike was enough to earn All Boys its first victory of the campaign - 1-0 at home to Olimpo.