The Reds had tied the game up in the sixth on back-to-back homers of their own, with Joey Votto and Brandon Phillips going deep with one out in the frame.
Weathers came on after two innings from Nick Masset. He got Chris Iannetta to a 3-2 count before he made a mistake pitch. And he paid dearly for his slider.
"We've found every way to lose a ballgame," Weathers said. "No one's pointing figures, because really no one can. It's been a collective unit that hasn't done their job. Tonight, I didn't do mine."
On the very next pitch, Weathers gave up another blast -- a homer to Carlos Gonzalez to right field.
"We actually got killed by the bottom of the order," Reds manager Dusty Baker said. "We knew they had a potent offense, but we didn't expect to get beat by the bottom of the order with the big boppers they have in the middle."
The Reds, meanwhile, couldn't come up with the same clutch hitting. After they had come back in the game thanks to the Votto and Phillips homers, they were shut down over the final two innings.
With the trades of Jerry Hairston Jr. to the Yankees and Edwin Encarnacion to the Blue Jays before Friday's Trade Deadline, the Reds struggling offense was relegated to even more bench players.
Utility player Drew Sutton started in left field for his first start of the season. Adam Rosales started at third base. Laynce Nix played center field in place of Willy Taveras. With so many players in different positions, it's safe to say the arrival of Scott Rolen can't come soon enough. Rolen was traded from Toronto on Friday.
"It will be a welcome sight to see him tomorrow," Baker said.
Another player making his first start in a new role was Justin Lehr. His first career start was cut short by walks, and through five innings he had thrown 97 pitches. He gave up two runs in the first and one run in the second after he walked the bases loaded. He left with the Reds trailing, 3-1.
"I think that's uncharacteristic for me," Lehr said of the walks. "I know when I do feel comfortable, I'm going to eliminate a lot of my wasted pitches."
Despite so many unfamiliar faces in the lineup, the Reds had a chance to take the lead in the seventh with the game tied at 3. With two outs, Sutton walked and Rosales reached on an infield single. That brought Votto to the plate. But the Cincinnati slugger flied out to center field.