In Uruguay, Nacional went down to a shock 2-0 defeat against modest River Plate, allowing Danubio to pull level with them at the top of the championship's first stage with one match to go.
COLOMBIA
Victor Cortes scored a second-half goal as America took a big step towards winning their 13th championship and equalling the record held by Millonarios.
Cortes turned in Pablo Armero's pass to finish off a counter-attack in the 63rd minute and silence the Atanasio Girardot stadium.
Medellin had more possession but rarely threatened Adrian Berbia in the America goal.
America, who dominated Colombian football during the 1980s but have more recently been hit by financial problems, also reached the final of the Apertura championship in the first half of the season before losing to Boyaca Chico.
Their most recent title was the 2002 Apertura.
The best features, fun and footballing quizzes, straight to your inbox every week.
Medellin coach Santiago Escobar, whose brother Andres was murdered in 1994 shortly after scoring an own goal at the World Cup in the U.S., said his team would not give up.
"I have full confidence in my team," he said. "We can still turn this result around. We are going to Cali to make a game of it."
URUGUAY
Danubio pulled level with Nacional at the top of the championship's first stage after both teams failed to win.
Both have 29 points from 14 games while third-placed Racing, who won 4-1 at Villa Espanola and are two points behind, also have a chance.
Nacional slumped to a 2-0 home defeat against River Plate, led by flamboyant former Uruguay coach Juan Ramon Carrasco.
Henry Gimenez gave Danubio a a first-half lead and was the most dangerous player on the field until he was bizarrely substituted by Carrasco in the 43rd minute after being booked.
Carrasco often substitutes players who are given yellow cards as part of his unusual disciplinary code.
Nacional attacked desperately in the second half only for Nicolas Nicolay to snatch a second for River in the last minute.
Danubio twice led against Central Espanol before being pegged back for a 2-2 draw.
Diego Ifran headed them in front but Fabian Coelho levelled with a penalty before the match swung Danubio's way near the half hour when Central keeper Sebastian Sosa upended Ifran in the area and was sent off and Sergio Leal converted the penalty.
But Central levelled again in the 72nd minute when Francisco Silva headed in from a corner.
Danubio had Damian Malrrechaufe dismissed and Central finished with nine men when Guillermo Firpo was sent off.
