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.
Linebacker Myles Jack, who suffered a season-ending knee injury, said Thursday he decided to leave UCLA and enter the 2016 NFL draft because he wants to be compensated for his skills.
The tougher tests await down the road for No. 3 Baylor Bears, but coach Art Briles has seen enough of his Bears to know this is his best team.
A decision has been made that Randy Edsall will not be the football coach at Maryland next season, and discussions are taking place about how and when to separate, a source said Thursday night.
Florida State running back Mario Pender has been released from the hospital but could be given a medical redshirt if he cannot return to the field this season.
Tennessee chancellor Jimmy G. Cheek has issued a statement amid rumors that alleges coach Butch Jones fought and punched senior offensive lineman Mack Crowder during a fall practice session.
With the addition of a few tweaks, UConn football coach Bob Diaco is still planning to bring a rivalry trophy with him to Florida on Saturday when the Huskies play UCF.