Guilherme Guido focused on backstroke, and today both he and Cielo are great Brazilian and South American swimmers.

The ISL is an annual professional swimming league featuring a team-based competition format with fast-paced race sessions.

At 17 years old, Guido participated in his first major international tournament, the 2004 FINA World Swimming Championships (25 m), in the city of Indianapolis, in October 2004.

He finished 4th in the 4×100-metre medley,[3] breaking the South American record with a time of 3:33.02, along with César Cielo, Kaio Almeida and Eduardo Fischer.

[17] He came fourth in the 4×100-metre medley with the Brazil team, in a race where the top four relays beat the world record of the United States from Beijing 2008.

[28] At the 2010 FINA World Swimming Championships (25 m), Guido, along with César Cielo, Felipe França and Kaio Almeida, hit the South American record of 4×100-metre medley with 3:23.12 time, getting the bronze medal.

[42] At the 2014 Pan Pacific Swimming Championships in Gold Coast, Queensland, Australia, he finished 4th in the 4x100-metre medley relay, along with Marcelo Chierighini, Felipe França and Thiago Pereira, and 8th in the 100-metre backstroke.

[43] At the 2014 FINA World Swimming Championships (25 m) in Doha, Qatar, Guido won a gold medal in the Men's 4 × 50 metre medley relay, formed by Guido, Felipe França Silva, Nicholas Santos and César Cielo, considered the "Dream Team" by Cielo (formed only by medalists or world champions in their respective individual events).

[44] On December 7, Guido won his second gold in the Men's 4 × 100 metre medley relay, along with César Cielo, Marcos Macedo and Felipe França Silva, with a time of 3:21.14, South American record.

It was established that there would be a swim-off between them; however, Guido chose not to swim the race, preferring to rest and focus on the 4 × 100 medley relay.

[67] At the 2018 FINA World Swimming Championships (25 m) in Hangzhou, China, Guido won a bronze medal in the Men's 4 × 50 metre medley relay, along with César Cielo, Felipe Lima and Nicholas Santos.

[70] In the Men's 100 metre backstroke, he broke two times the South American record in short course: 49.57 at heats[71] and 49.45 at semifinals,[72] finishing 5th in the final.