Both were named on Tuesday in the country's 23-man squad for the tournament along with Juventus forward Paulo Dybala, who made the cut despite scoring only five goals in 30 league appearances this season.
- Info Page: All you need to know about the 2019 Copa America
There was no place for Inter Milan striker Mauro Icardi, the Nerazzurri's leading scorer this term with 11 goals.
Messi, who took a nine-month break from the national team after the World Cup before playing again in a 3-1 defeat to Venezuela in March, has scored 50 goals in all competitions this season for Barcelona heading into Saturday's Copa del Rey final against Valencia.
The Argentina captain finished as La Liga's top scorer with 36 goals in 34 appearances as Barca retained the Spanish crown.
Argentina director of national teams Cesar Luis Menotti said in Tuesday's news conference that "Messi is among the greatest in the history," while Scaloni hailed the strength of his squad.
"We believe that we have selected the best players right now for what is an important time for the national team," Scaloni said. "It causes me pain for those that haven't made it but I could only select 23.
"When you have so many good players to choose from, there are always doubts. But I made my decisions on what was best for the team. We know what we want and we know what our path has to be."
Scaloni added: "I spoke to Messi regarding what our week of training here would be like. We only spoke about planning."
Aguero was a big contributor to City's successful Premier League title defence, scoring 21 goals and setting up eight more in 33 league appearances.
Scaloni had previously not selected Aguero, 30, since replacing Jorge Sampaoli as manager after the World Cup.
On selecting Aguero for the first time since taking over the national team, Scaloni said: "My opinion regarding Aguero has not changed. We wanted to give others an opportunity to try. But Kun's numbers speak for themselves. We are very happy that he is with us.
"The only thing we hope is that we can put the pieces together so that he can do with us what he does at his club."
Aguero last featured for Argentina as a substitute in their 4-3 loss to France in the round of 16 in Russia. Paris Saint-Germain midfielder Angel Di Maria, who also returned to the fold in March, is among the veterans included.
River defender Milton Casco was a surprise inclusion in the squad. To make room, Scaloni left out Sevilla defender Gabriel Mercado and selected Casco, 31, who last featured for Argentina in 2015.
"Casco is a player that play on both flanks," he said. " We have monitored him and felt he could give us solutions."
Scaloni added he is an admirer of 21-year-old Tottenham centre-back Juan Foyth, for whom he professed "blind faith" in.
Of Dybala's addition, Scaloni said he is hoping to have the Juve forward at his best.
"Dybala is not going through the best end of the season but we spoke to him and we trust him," he said. "He is stll a great player and we need for the best to be here."
Injuries have deprived Argentina of Gremio defender Walter Kannemann and Racing Club winger Matias Zaracho.
Icardi was left out despite being his club's top scorer with five more goals than teammate Lautaro Martinez, who has been selected in the Argentina squad.
A contract dispute with his club earlier this year saw Icardi dropped from the team for 53 days and he has only scored twice since returning to play on April 3.
Martinez has not scored since March 17.
Scaloni has included seven Argentina-based players, among them River Plate veteran goalkeeper Franco Armani. The Albiceleste last lifted the Copa America in 1993 -- the last major tournament the senior side has won -- and begin the tournament against Colombia on June 15. They will also take on Paraguay and Qatar in Group B.
Argentina will begin training on May 27.
Argentina full squad:
Defenders: Juan Foyth (Tottenham), Nicolas Otamendi (Manchester City), German Pezzella (Fiorentina), Nicolas Tagliafico (Ajax), Ramiro Funes Mori (Villarreal), Renzo Saravia (Racing Club), Marcos Acuna (Sporting Lisbon), Milton Casco (River Plate).
Midfielders: Leandro Paredes (Zenit), Guido Rodriguez (Club America), Giovani Lo Celso (Betis), Exequiel Palacios (River Plate), Roberto Pereyra (Watford), Rodrigo De Paul (Udinese), Angel Di Maria (PSG).
Forward: Lionel Messi (Barcelona), Sergio Aguero (Manchester City), Lautaro Martinez (Inter Milan) Paulo Dybala (Juventus), Matias Suarez (River).