Canada started slow on Day 8 of the Games before rebounding to win 12 medals, including three gold.
But the powerful Americans surged ahead Saturday with 10 gold medals and 21 overall.
The U.S. now has 50 gold, 41 silver and 44 bronze medals to lead both the gold and overall table.
Canada is second in both categories with 48 gold, 41 silver and 33 bronze. The hosts, which have already eclipsed their gold and overall totals from the 2011 Pan Am Games, are still well on their way to their goal of finishing in the top two overall. Brazil is well back in third with 28 gold and 86 overall medals.
Canada was led on Day 8 by gold medals from the men's softball team, cyclist Hugo Barrette and veteran swimmer Ryan Cochrane.
The softball team capped a slow afternoon for Canada with a 2-1 win over Venezuela for their eighth straight Pan Am gold.
Brad Ezekiel provided the heroics with a game-winning two-run home run to left-centre in the sixth inning.
Pitcher Sean Cleary settled down after some early control issues and kept Venezuelan hitters off-balance until the seventh. He gave up a run then but held on.
"We wanted to bring a swagger back to Canada and I think we've done that," Canada coach John Stuart said, adding it was particularly satisfying to win gold on home soil.
"It's history. It's never been done before. That's something these guys can be very proud of," he said.
After Canada completed the final out, Venezuelan players weren't happy about how the Canadians were celebrating and tempers briefly flared.
"That's a shame. It put a damper on our celebration," Stuart said. "That's their problem to deal with. I don't know what happened. I was just trying to get our guys off the field to celebrate and enjoy the moment."
Later, Barrette continued Canada's dominance in track cycling, winning gold in the men's sprint.
The native of Cap-aux-Meules, Que., swept Trinidad and Tobago's Njisane Phillip 2-0 in the best-of-three final. Barrette clinched the victory with a perfectly executed slip move underneath to pass Phillip and take a lead he'd never relinquish.
"I wanted the front, I took the front," he said. "I was confident, I wanted to win for the home crowd."
Canada has five gold medals so far on the track at the velodrome in Milton, Ont.
Canada closed out the swimming competition with four medals Saturday, including a gold for Victoria native Cochrane in the men's 1,500-metre freestyle.
Cochrane set a new Pan Am record by winning in a time of 15 minutes 6.40 seconds.
It's the second gold of the Games for Victoria native Cochrane, who won the men's 400 freestyle on Friday.
"I sang O Canada both times fairly loudly," Cochrane said. "It's one of the best sporting experiences of my life. It ranks up there with winning an Olympic medal because winning at home and the 'Go Canada' chants, you don't find that everywhere."
The women's 4x100 medley relay team took silver, while Sydney Pickrem earned a bronze medal in the women's 200 individual medley. The men's 4x100 relay added another bronze.
Canada finished with eight gold, 10 silver and nine bronze in swimming competition, holding its own against powerful teams from the U.S. and Brazil.
Canadian freestyle wrestlers added three medals on Saturday.
Arjun Gill of Quesnel, B.C., took silver in the men's 97 kilogram, Korey Jarvis of Eliot Lake, Alta., earned the silver in the men's 125 kg and Toronto's Tamerlan Tagziev took bronze in the men's 86 kg.
Canada finished wrestling competition with eight medals — three gold, three silver and two bronze.
Earlier, Lee Parkhill of Oakville, Ont., won bronze in the men's laser sailing, finishing the race with 12 points.
Vancouver rhythmic gymnast Patricia Bezzoubenko won a bronze medal in the individual all-around competition, holding on to third place despite dropping the ribbon early in her final routine at the Toronto Coliseum.
Bezzoubenko won five gold medals at last year's Commonwealth Games in Glasgow.
Winnipeg's Jay Lyon won bronze in the men's individual archery competition, defeating American Zach Garrett 6-0 in the third-place match.
There will be more medals on the way for Canada, as the men's baseball team advanced to the final with a 7-1 win over Puerto Rico.
Elsewhere, Canada beat Cuba 71-68 in women's basketball to set up a semifinal meeting with Brazil.
Canada's women's beach volleyball team advanced to the semifinals with a 2-0 rout of Costa Rica, while the women's volleyball team won a 3-1 preliminary-round match against Cuba.