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.
Running back Devontae Booker had 124 combined yards and a touchdown and Utah spoiled Jim Harbaugh's Michigan coaching debut, beating the Wolverines 24-17 on Thursday night.
ESPN 300 running back Elijah Holyfield, the son of former heavyweight boxing champion Evander Holyfield, has decided to stay home and attend Georgia, he announced Friday.
Arizona star linebacker Scooby Wright will have an MRI after injuring his left knee in the first quarter of the Wildcats' season-opening 42-32 win over UTSA on Thursday night.
Miami reserve linebacker Al-Quadin Muhammad has been suspended for the season opener against Bethune-Cookman on Saturday for a violation of team rules, a source confirmed to ESPN.com
Trevone Boykin threw for 246 yards and a touchdown and ran for 92 yards and another score to help No. 2 TCU outlast Minnesota 23-17 on Thursday night.
All-American defensive end Shawn Oakman and safety Orion Stewart have been suspended for Baylor's season opener Friday against SMU for a violation of team rules, a school spokesman told ESPN.com.