The violence broke out inside and near the city's National Stadium ahead of a scheduled match between the Olimpia and Motagua clubs.
The violence is believed to have started when Olimpia supporters attacked the Motagua team bus with stones and sticks. "Bottles, stones were thrown at us and the players threw themselves on the floor screaming," Diego Vásquez, Motagua coach, told Honduran media.
Three Motagua players --- Emilio Izaguirre, Jonathan Rougier, and Roberto Moreira -- were injured by shards of broken glass and transferred to a private hospital to receive medical assistance, according to the team's social media.
The Honduran National Police said that fans of the rival teams rioted following the attack on the bus. "Fans of both teams staged a confrontation on the outskirts of the stadium, so they (police) proceeded with the use of deterrent means," police said, adding that tear gas was used.
Laura Schoenherr, a spokeswoman for the city's Hospital Escuela Universitario, confirmed that numerous fans were injured in the incident. "Three people died and seven were shot and stabbed. One of them is a boy. Three of the injured adults are in critical condition," she told Reuters.
Police also implemented emergency procedures inside the stadium, moving around 10,000 fans to the center of the pitch in a bid to halt attendees from stampeding towards the exit and being caught up in tear gas outside the stadium.
The National Football League of Honduras subsequently canceled the game, which 20,000 fans had been expected to attend.
"This has to be severely sanctioned by the corresponding authorities," Motagua club wrote on Twitter. "Reprehensible and lamentable," it added in another.
Rafael Villeda, president of Olympia, told Honduran media that the violence was "unfortunate" and said he would meet with the leadership of Motagua and the National League to decide on the future of the match.
Saturday's clashes were not the first time that violence has broken out between Motagua and Olimpia fans. In 2009, a brawl between supporters left two dead and more than 15 injured. In 2016 another confrontation caused one death.
Olimpia and Motagua are the two most successful football teams in Honduras, and their rivalry is seen as the biggest in the country.
CNN's Matthew Robinson contributed to this report.