Micheal Warren had 17 points and seven boards, and Jason Richardson added 14 points for the Matadors (2-2), who shot 50.8 percent from the field, 75 percent from the free-throw line, and had 21 assists.
Cal State Northridge opened on an 11-2 run and extended its lead to double digits with an Ajayi layup midway through the first half en route to a 39-26 halftime lead.
The Matadors kept the pressure on throughout much of the second half, opening up a 20-point lead (53-33) on a Richardson 3-pointer with 13:54 left. Antonio Bishop made a layup with 8:31 remaining which cut Vanguard deficit to 58-44, but the Lions got no closer.
Jaamon Echols scored 16 to lead Vanguard. Zach Allmon had 10.