The players -- upset with travel policies, poor facility conditions and a tumultuous coaching situation -- made a decision not to play at a team meeting Friday afternoon, a player told ESPN's Brett McMurphy.
"We aren't playing," the player said.
Jackson State spokesman Wesley Peterson told The Associated Press on Friday that Grambling officials contacted JSU at about 6 p.m. ET and informed the school of the decision.
The Southwestern Athletic Conference issued a statement late Friday that ruled the game a "forfeit," charging "Grambling State the loss and awarding Jackson State with a win."
Grambling officials met throughout a chaotic Friday, trying to rectify the sour situation between players and administration. Apparently, nothing could be worked out so that the game could be played.
Grambling spokesman Will Sutton said late Friday that university officials would have no further comment. He said players will not be available for interviews.
Buses that lined up at Grambling to transport the team remained empty Friday.
School officials delayed departure of the team buses for an hour, until 4:30 p.m. ET, in hopes of changing players' minds, according to reports. That deadline passed and the buses left without players before 5 p.m., The News-Star reported.
SWAC commissioner Duer Sharp said according to league rules, Grambling will forfeit and the school will be fined. Grambling athletics director Aaron James said Friday night that the school will be fined $20,000 by the SWAC, according to USA Today Sports.
"I've been in contact with the schools and they informed me the game is going to be canceled," Sharp said. "It's just a very disappointing situation when something like this happens. But we'll do everything we can with these schools to reach an understanding moving forward."
Grambling players walked out of a meeting with school officials Tuesday and did not show up at practice Wednesday.
On Thursday, the school relieved George Ragsdale of his duties as interim coach and replaced him with defensive coordinator Dennis "Dirt" Winston.
The Shreveport Times reported that one of the conditions for the players to end their boycott was that Ragsdale, who started the season as running backs coach, be relieved of his coaching duties.
Athletic director Aaron James said Winston has the ability to "tone things down and get the program up and running smoothly."
According to the Times, the players met with administrators Tuesday to voice concerns about traveling by bus instead of plane to games in Kansas City, Mo., and Indianapolis, poor facility conditions and the firing of coach Doug Williams in September.
Williams sent a text message Friday evening to USA Today, saying: "I'm proud of them boys. They took a stance."
For the 750-mile trip to a neutral-site game in Indianapolis, SI.com reported that the team left campus at 6 p.m. last Thursday and arrived in Indianapolis at 9 a.m. Friday. Grambling lost 48-0 to Alcorn State the next day. Alcorn State, based in Mississippi, flew to the game, Grambling safety Naquan Smith told SI.
"It does something to your body, being on the bus that long," Smith told SI. "We were kinda upset [the] other team got a chance to fly there. It wasn't fair."
For this week's game, Jackson, Miss., is about 160 miles from Grambling, La.
Grambling fired Williams in September after the Tigers (0-7, 0-4 SWAC) lost their first two games by a combined score of 71-19. Grambling went 1-10 last season.
Williams had raised funds through an alumni group and bought sorely needed new mats for the weight room, SI reported. The old mats presented safety hazards, but since the raised money had not gone through the school's foundation, the school president and athletic director ordered the new mats to be stored in another building, according to SI.
Williams was fired a week later.
The game is Jackson State's homecoming and could hurt the school financially. The Grambling-Jackson State matchup usually draws very well -- an announced crowd of more than 21,000 attended the game in Jackson in 2011.
Jackson State spokeswoman Jean Cook said the school would still have homecoming festivities, featuring the homecoming parade, a football scrimmage and extended band performance. The school said it's working on a process to refund tickets.
"It's not ideal," Cook said. "But we're trying to make the best of things."
Late Friday, the University of Louisiana System, which oversees nine state universities including Grambling, released a statement on behalf of system president Sandra Woodley and Board of Supervisors chairman Wayne Parker, who said they have been "closely monitoring" the situation at Grambling.
"The student athletes are our primary concern, and while we respect their right to protest, we are concerned about the unintended consequences resulting from this action," the statement read. The statement added that the university system is working closely with Grambling president Frank Pogue, the NCAA, and other advisers "to proceed in a compassionate manner that minimizes potentially harmful ramifications for our students and demonstrates pride and dignity for Grambling."
Louisiana state senator Rick Gallot, a Democrat from Ruston and a Grambling graduate, says he hopes a resolution can still be reached.
"I am still optimistic that not only will the situation with the scheduled game with Jackson State be resolved and the teams will play, but I am also optimistic that leadership issues and the concerns of the student-athletes will all be fleshed out and addressed and we'll be able to return to a semblance of normalcy on campus," Gallot said.
Information from The Associated Press was used in this report.