The win snapped Fisher's 40-game, regular-season home winning streak and marked just the fourth victory for Nazareth in the last 31 meetings.
With the game tied at 60, Fisher's Dan McSweeney missed two free throws.
Nazareth's Ryan McAdams grabbed the rebound after the second miss,went up the court, and passed the ball to Kyle Nelson, who was in the left corner with two seconds left. Nelson then dished the ball to a cutting Smith, who banked in a shot from the right block as the horn sounded.
McSweeney led the Cardinals (12-3 overall, 3-1 Empire 8), ranked 16th nationally, with 20 points, while Nick Bennett added 11 points and four steals. Justin Beigel tallied 11 rebounds, eight points and four blocked shots, while Sean O'Brien tallied nine rebounds, eight points and a career-high 12 assists.
Jeff DeHimer finished with 18 points for Nazareth (6-9, 3-1), while Matt Groot added 14.