"We learn from the good stuff and the bad stuff," Stafford said.
When all of the reserves for both teams took over in the second half, the Browns outscored Detroit 16-3.
Jeff Wolfert's 45-yard field goal with 28 seconds left won it for Cleveland after the Lions stopped Adonis Thomas on a two-point conversion with 6:05 left to keep the lead, but couldn't keep the ball to seal a win.
"Regardless of whether or not they count, it is always more fun to win," Cleveland coach Pat Shurmur said. "I told our guys that, and they made some plays to put us in position to do that."
"We followed league protocols," Shurmur said. "When he's healthy he will play again. Not before that."
Massaquoi was limited the past two seasons because of concussions, including one he had that knocked him out of a game last October.
The Lions didn't risk Stafford getting hurt for very long, allowing him to play less than a quarter.
Stafford is coming off a breakout season in which he threw for 5,000-plus yards and 41 TDs while ending the franchise's 11-year playoff drought.
His first drive of the preseason ended when Joe Haden broke up a pass. Stafford seemed to throw a pass early, sensing pressure that didn't appear to be there, and his pass intended for Brandon Pettigrew was picked off by Sheldon Brown to stop Detroit's second possession.
"I had to cut it loose earlier than I wanted to," Stafford said. "Pettigrew and I weren't on the same page."
Stafford provided a flashback to last year, throwing a 27-yard pass to All-Pro receiver Calvin Johnson, on his third and final drive that ended quietly at midfield.
Hill, who won't play much if Stafford stays healthy during the regular season, was 8-of-12 passing for 83 yards and a TD.
Backup kicker Derek Dimke's 40-yard field goal early in the fourth quarter gave Detroit a 17-10 lead.
Thomas ran for a 3-yard score to pull the Browns within a point and their defense got the ball back for fourth-string quarterback Thaddeus Lewis to lead the game-winning drive.
Weeden was 3-of-9 passing for 62 yards with an interception and a fumble.
"I know my numbers didn't look good, but I'm not a numbers guy," said Weeden, the No. 22 overall pick in the NFL Draft. "This was my first time out, and there was some good and some bad."
Weeden ended his first possession as a pro by fumbling, a turnover forced and recovered by Willie Young.
Detroit, meanwhile, seemed to get out of its first of four preseason games relatively healthy.
Kevin Smith got a shot to start at running back, gaining 28 yards on five carries, and might have to hold off Williams, who had 69 yards rushing and a TD on eight attempts to keep the job.
The Lions have been looking for a cornerback to replace their only starter missing on defense, Eric Wright -- who signed with the Tampa Bay Buccaneers -- and the search will likely end with rookie Bill Bentley. The third-round draft pick got beat on Weeden's perfectly thrown, 34-yard pass to Travis Benjamin on his third snap as a pro. But Bentley bounced back by intercepting a pass and breaking up another attempt.
"Let's be clear: preseason games, we don't use them as a barometer," Detroit coach Jim Schwartz said. "But you want to play well, and I don't think we played well on offense, defense or special teams from the beginning to the very end."
Copyright 2012 by The Associated Press