Hall officials estimated it had about 4,000 visitors after its admission price was cut to $2 for the final days on Saturday and Sunday.
The closing comes three years after the National Football Foundation announced the Hall of Fame would move from South Bend following years of low attendance. It moved from Ohio to the site a few miles from the University of Notre Dame campus in 1995.
Mark Maurer, the hall's operations director, said it was interesting to have the large crowds on hand.
"There has been so many people passing though, time just seems to fly by," Maurer told the South Bend Tribune. "It's sad because for me, you wonder where everyone has been before today."
City officials are trying to sell the 58,000-square-foot facility for $2.8 million, even though the city is still paying off $6.4 million of the $18 million in bonds it issued to build the museum.
Mayor Pete Buttigieg said another museum or similar exhibition might be ideal for the building, with the next best options possibly office or retail space that would bring people downtown.
Hall of Fame visitor John Milliken said he was disappointed that the museum was closing.
"What a beautiful building, what a beautiful place for downtown South Bend, and you hope like heck that they don't tear the building down," Milliken told WSBT-TV.
City officials had projected that the hall would attract 200,000 visitors a year. But attendance the first year was about 115,000 and about 60,000 annually after that.
Organizers initially expected the new Hall of Fame to open in Atlanta in 2012, but funding setbacks have delayed that until 2014.
Ken Stephens, the hall's historian, said the museum's last days were bittersweet.
"I do think we have been able to bring college football history to South Bend and it's sad to have to say goodbye to it all," he said.