Six players had touchdowns for the Huskies (8-2, 6-0 Mid-American).
Northern Illinois built a 28-0 halftime lead and then combined with the Rockets (6-4, 5-1) for a 51-point third quarter.
Harnish went 11-of-16 for 162 yards. He also rushed 13 times for 149 yards scored on a 28-yard run. Spann added 70 yards on 20 carries.
Adonis Thomas had 10 carries for a game-high 152 yards, including touchdown runs of 18 and 60 yards, for Toledo. Quarterback Terrance Owens was 18-of-38 for 186 yards, two touchdowns and an interception. Eric Page had seven catches for 67 yards.
Northern Illinois' 65 points were a season high and fifth-highest in school history and its seven-game winning streak is the longest since 2003. Toledo's loss was its first in four games.
Spann rushed for 44 yards on nine carries on a 14-play opening drive -- including a 1-yard touchdown run -- as the Huskies opened a 7-0 lead.
On its third possession, Northern Illinois took a 14-0 lead as freshman wide receiver Akeem Daniels capped a 12-play, 74-yard drive with a 12-yard touchdown run.
The Huskies added two touchdowns in the final 5:43 of the half as Harnish threw a 33-yard scoring pass to Nathan Palmer. With 20 seconds left, Harnish capped a six-play, 80-yard drive with a 28-yard touchdown run.
Toledo broke the shutout with a safety early in the third quarter. Two minutes later, Thomas scored on an 18-yard touchdown run that trimmed the deficit to 28-9.
Harnish then set up a score with a 69-yard run to the Toledo 11. Three plays later, Spann scored on a 5-yard run for a 35-9 lead.
Toledo and Northern Illinois then traded big-play touchdowns.
Thomas had a 60-yard scoring run while Daniels had a 50-yard run for a 42-16 Huskies lead with 5:44 left.
Spann's third touchdown came with 2:34 left in the third on an 8-yard run.
The Rockets then scored on a 3-yard pass from Owens to Page.
Northern Illinois' Tommy Davis had an 83-yard kickoff return for a touchdown for a 56-23 lead.
Senior Michael Cklamovski hit a 43-yard field goal to open the fourth-quarter scoring.
Jasmin Hopkins extended the lead to 65-23 with a 55-yard touchdown run with 1:37 to play.
Toledo scored on a 3-yard pass from Owens to Jerome Jones with three seconds left.