[4] Continuously ranked in the world's top-100 between July 2013 and March 2021, and with four ATP Tour singles titles,[4][5] Sousa is often regarded as the best Portuguese tennis player of all time.

In 2001, he won the national under-12 singles title, beating future Davis Cup partner Gastão Elias in the semifinals, and was runner-up in doubles.

[31] In September 2004, aged 15, Sousa moved to Barcelona, Spain, to attend a boarding school and join the Catalan Tennis Federation.

[36] He played two singles dead rubbers, winning over Cyprus' Eleftherios Christou in July and losing to Ukraine's Illya Marchenko in September.

[38][39] At the Estoril Open, Sousa was granted a wild card to participate in his first doubles ATP World Tour level tournament, but lost in the first round.

[39] During 2009, Sousa was twice called to the Portugal Davis Cup team, winning both singles dead rubbers he took part in – over Philippos Tsangaridis from Cyprus in March and Algeria's Sid-Ali Akkal in July.

[16] At the Davis Cup, Sousa played two more dead rubbers, winning for the second time in three seasons over Cyprus' Christou and losing to Bosnian Damir Džumhur.

[18] At the ATP World Tour, Sousa participated as a wildcard in the singles and doubles events in Estoril, losing in the second round of the former to Canadian Milos Raonic.

[31][16] Once again, Sousa was called for two dead rubbers at Davis Cup, winning over Martin Kližan from Slovakia and losing to Switzerland's Marco Chiudinelli.

99, and Sousa became the fourth Portuguese player to enter the ATP top-100 singles ranking after Nuno Marques, Frederico Gil and Rui Machado.

[61][62] Later in the season, Sousa showed uncertainties about his future Portugal Open participation, which prompted tournament director João Lagos to comment on the contention.

[64] Sousa returned to action at the Madrid Masters qualifying rounds and at his first Challenger tournament of the season in Bordeaux, but he lost early in these attempts.

[70] In July, he played exclusively in Challenger tournaments, being runner-up in singles and doubles in San Benedetto,[48][70] re-entering the top 100 rankings, which he has maintained ever since.

[88] Sousa beat Frenchman Julien Benneteau in three sets in the final after saving one match point, becoming the first Portuguese player to win an ATP World Tour singles tournament.

[119] To cap his grass court season, Sousa played his first ever Wimbledon Championships main draw match at the 2014 edition, with a straight sets loss in the first round to world No.

[121] In the doubles competition, he partnered with Argentinian Carlos Berlocq to play a four-hour, five-set first round loss to Martin Kližan and Dominic Thiem.

[122] In July, Sousa reached his second-career ATP tour level final and his first of 2014 at the Swedish Open, defeating the defending champion Carlos Berlocq in the semifinals.

[132] In the doubles competition, Sousa partnered with Serbian Dušan Lajović and beat the Americans Marcos Giron and Kevin King in the first round.

[149][150][151] In the doubles competition, Sousa partnered with Santiago Giraldo to reach the second round, where they lost to 2nd seeds Julien Benneteau and Édouard Roger-Vasselin.

[162][163][164][165] At the Geneva Open, Sousa won a first round match over his Brazilian homophone João Souza, which was notable for the umpire needing to refer to each player by their nationality to distinguish between them during the calls.

After beating four higher-ranked players, including Benoît Paire, Sousa defeated 7th seed Roberto Bautista Agut in the final in three sets.

[190] After training at Rafael Nadal's home ground in the pre-season, Sousa began the 2016 season with a first-round loss to Fabio Fognini at the Auckland Open.

[195] In April, Sousa reached his first Masters 1000 quarterfinals at the Mutua Madrid Open 2016, after beating Nicolas Mahut, lucky loser Marcel Granollers and Jack Sock.

At the 2016 Olympic Games in Rio de Janeiro, Sousa won his first match but lost in the next round in three sets to eventual silver medalist Juan Martín del Potro.

He started the 2017 season at the 2017 Auckland Open once again, where he reached the final after beating Albert Ramos Viñolas, Brydan Klein, Robin Haase and Marcos Baghdatis.

Sousa's January ended with a first-round exit at the Australian Open, having lost in five sets to Jordan Thompson, his worst result at this Grand Slam since 2014.

One of these includes two crucial defeats in the Davis Cup where Portugal could have qualified for the World Group for the first time in its history, specially considering the absence of the Zverev brothers and Kohlschreiber.

63 on 23 May 2022 by moving 16 spots up,[200] after reaching his second final of the season at the 2022 Geneva Open without dropping a set, earning his biggest win in three years over World No.

As of October 2013, Sousa has been represented by Polaris Sports, a subsidiary of Jorge Mendes's Gestifute, which manages the career of other major Portuguese sportspeople, including Cristiano Ronaldo.

[212][213] Sousa uses a Wilson racquet,[214] and is endorsed by Lotto Sport Italia since January 2014, in a two-year partnership which covers the supply of footwear, clothing and accessories.