In 1926 professionalism came to the Hungarian football scene, with the unfortunate result that Bocskai FC was formed using players from DVSC and city rivals DKASE and DTE, with the result that Bocskai FC ruled the football roost in Debrecen for 15 years while DVSC continued to struggle in the lower divisions.
In 1940 the professional/amateur division of players was abolished and Bocskai FC suffered financial collapse, returning DVSC to top-dog position in the city.
Although the team was relegated from top flight football in 2001 as a result of questionable refereeing on home matches (Ref.
Béla Kiss was helped to escape from the stadium by officials in order to avoid the crowd's anger after the match against Budapest Honvéd FC), the then promoted BKV Előre SC could not afford to play in the first league in lack of the necessary financial conditions, thus DVSC remained in the top flight as the better relegated team according to the rules and regulations of the championship which led to some controversy whether it was just.
Debreceni VSC beat Dnepr Mogilev, FC Hradec Králové, Hansa Rostock, and lost to Ruch Chorzów in the semi-finals.
Although Debrecen beat the German club 2–1 at home, they lost 2–0 in the away-game, and their first UEFA Cup season ended.
Therefore, in 2001 Debrecen they could enter the UEFA Cup 2001-02 where they beat the Moldovan club Nistru Otaci 3–1 on aggregate in the first round.
[3] Debrecen's first successful UEFA Cup career was ended in the third round when they faced with the Belgian Club Brugge.
The first match in the UEFA Champions League 2005-06 qualifiers was played in 2005 against the Croatian club, Hajduk Split.
In the next round Debreceni VSC had to face one of the best teams in Europe, Manchester United and lost 0–6 on aggregate.
In the first leg (15 September 2005) the Ukrainian club beat Debrecen 4–1 in the RSC Olimpiyskiy stadium in Donetsk, Ukraine.
Debrecen managed to duplicate the feat and win the Hungarian National Championship I 2005-06, after in the last round on 3 June, they defeated Pápa 4–1, and the then the leader of the league Újpest (who had the same number of points as Debrecen but had more away wins) lost to Fehérvár in a climactic battle ending in 3–1, which also caused Fehérvár to place 3rd.
[9] In the Hungarian National Championship I 2006-07 season Debrecen became again champion on the 28th match-day beating Rákospalotai EAC on home turf.
The Swedish club won the first leg by 1–0, while a goalless draw in Sweden was enough for Elfsborg to go through the third qualifying round.
In the first round of the Central-East region they drew in Kazakhstan against Shakhter Karagandy 1–1, while in the second leg they beat the Kazakh team by 1–0.
On 15 July 2009 Debreceni VSC beat Kalmar FF 2–0 at home by the goals of Kiss and Varga.
As a consequence, Debreceni VSC won the Hungarian National Championship I 2009–10 despite losing to Kecskeméti TE in the last round.
[27] On 1 May 2012 Debrecen beat MTK Budapest on penalty shoot-out in the 2011–12 season of the Hungarian Cup final winning the trophy for the fifth time.
On 15 July 2014, the first leg ended with a goalless drew against Cliftonville at Solitude in Belfast, Northern Ireland.
In the 2016–17 Nemzeti Bajnokság I Debrecen finished their contract with Elemér Kondás and he was replaced by András Herczeg as an interim coach on 25 July 2016.
[44] On 22 May 2017, Pontes left the club with mutual agreement and he was replaced by András Herczeg for the last round against Diósgyőri VTK to escape from the relegation.
At the end of the season, Gábor Szima, the owner of the clubs, also sold his shares to the local government of Debrecen.
In the summer of 2020, Debrecen signed some of their former players including Mihály Korhut, József Varga, Ádám Pintér, and Bence Sós.
[55] In February 2021, the new management debuted in the 2020-21 Nemzeti Bajnokság II beating Szeged-Csanád Grosics Akadémia 5–0 at the Szent Gellért Fórum.
[56] On the 26th match day, on 27 February 2021, Debrecen suffered a shocking defeat (1−2) against Vasas SC at Nagyerdei Stadion.
[57] On 9 March 2021, Hungary national football team and former Szombathelyi Haladás, Budapesti Honvéd FC player, Roland Ugrai, was signed by the club.
[59][60] On 25 July 2021, Debrecen played against Serie A club A.S. Roma at the Stadio Benito Stirpe in Frosinone.
[61][62][63] On 31 July 2021, on the first match day of the 2021–22 Nemzeti Bajnokság I season Debrecen were hosted by Budapest Honvéd FC.
[72] Although Debrecen started the 2024–25 Nemzeti Bajnokság I season with a 3–0 away victory against Győr on 2 August 2024,[73] in the following three matches the club could collect only one point against Kecskemét (1-1)[74] and lost to Diósgyőr (1–0)[75] and Újpest (3–0).
[78] On 28 September, Máté's debut at the Nagyerdei Stadion ended with a 3–2 defeat against MTK Budapest FC.