[3] Vydra previously played for FC Chotěboř, Vysočina Jihlava, Baník Ostrava, Club Brugge, Udinese, Watford, Derby County and Burnley.

In June 2010, Vydra moved to Serie A side Udinese and was also voted by sports journalists the Czech Revelation of the Year for his performances at Baník Ostrava in the 2009–10 season.

[12] Vydra's season at Watford finished in disappointment as his club lost the chance to be promoted to the English top-flight after losing the play-off final against Crystal Palace and he injured his ankle during the match, having to be substituted at half time.

[13] Vydra joined Premier League club West Bromwich Albion on a season-long loan deal on 13 August 2013.

[14] He scored his first goal for the club on 21 December 2013, equalising for West Brom in a 1–1 Premier League draw against Hull City.

[18] Vydra made a scoring return as he netted in Watford's 3–0 opening day win over Bolton Wanderers on 9 August 2014.

[22] He started the 2015–16 season behind Odion Ighalo and Troy Deeney in the pecking order, on 25 August 2015, he played for Watford in a 1–0 loss against Preston in the League Cup.

[28] On 27 August 2016, Derby County announced that they had signed Watford striker Vydra on a four-year deal, for a fee reported at £8,000,000.

[41] In July 2018, Vydra held talks with fellow EFL Championship side Leeds United over a potential move.

[51] On 23 December 2022, Vydra returned to Czechia joining Viktoria Plzeň on a free transfer and signing a two-and-a-half years contract.