[18][19] On 16 May 2008, Santana joined Bundesliga club Borussia Dortmund, with a fee in the region of €2,000,000 and signed a five-year deal.

[20][21] Upon joining the club, Borussia Dortmund's sports manager Michael Zorc said about the match: "It doesn't cost one, but also not three million euros.

[26] After missing the next six matches due to injury, Santana returned to the starting line–up against Eintracht Frankfurt on 15 November 2008 and scored his third goal for the club, in a 4–0 win.

[40] As a result, Santana was dropped to the substitute bench between 19 September 2009 and 31 October 2009, though he started two times for Borussia Dortmund.

At the start of the 2010–11 season, Santana found himself placed on the substitute bench, as Mats Hummels and Subotić were continued to be Borussia Dortmund's first choice centre–backs by Manager Jürgen Klopp.

[75] At the start of the 2011–12 season, Santana formed a centre–back partnership with Hummels against rivals, Schalke 04 in the DFL-Supercup and played 120 minutes in a 0–0 draw, as Borussia Dortmund lost 4–3 in the penalty shootout.

[78][79][80] However, Santana suffered ankle injury that saw him recovered, but saw him placed on the substitute bench, with Hummels and Subotić continued to be the club's first choice centre–backs.

[84] Three weeks later on 23 November 2011, Santana made his first UEFA Champions League start, in a 2–1 loss against Arsenal.

[102] Prior to signing a new contract ahead of the 2012–13 season, Santana said that he had thought about leaving Borussia Dortmund, due to continuously being on the substitute bench.

[107][108][109] Santana made his first appearance of the season, starting the whole game, in a 3–0 win against FC Oberneuland in the first round of the DFB–Pokal.

[110] As part of Klopp's rotation plan, he was given an opportunity to get more playing time, making a number of starts in the absence of first choice centre–backs, Hummels and Subotić,[111][112][113] However, this left Santana unsatisfied with the role, due to his hopes of playing in the FIFA World Cup in his homeland country, Brazil.

[115] The second half of the season saw Santana receiving a handful of first team opportunities and formed a centre–back partnership with either Hummels and Subotić.

[116][117][118][119][120] On 3 March 2013, he scored the first UEFA Champions League goal in a 3–0 victory over Shakhtar Donetsk in the second leg of the last 16 with a header directly from a corner to advance to the next round.

[128] Despite being critical towards Klopp, Santana described leaving Dortmund for Schalke as a "hard decision", due to the rivalry between two clubs.

[129] On 28 May 2013, FC Schalke 04 confirmed that Felipe Santana had signed a contract with them until 30 June 2016, with the transfer fee was reported by media as €1,000,000 at the time.

[133][134] In a match against PAOK in the second leg of the UEFA Champions League play–off round, Santana started the whole game and helped Schalke 04 beat the opposition team 3–2 to advance to the group stage.

[146][147] He didn't make his return to the first team against Eintracht Frankfurt on 11 April 2014, coming on as an 82nd-minute substitute, in a 2–0 win.

[148] However, in a match against Freiburg on 3 May 2014, Santana was sent–off for a second bookable offence, as Schalke 04 won 2–0 to qualify for the UEFA Champions League next season.

[150] However, during a 1–1 draw against Bayern Munich on 30 August 2014, he suffered a tore his muscle bundle in the 81st minute and was substituted as a result.

[156] But he made his return to the first team, coming on as a second-half substitute, in a 2–1 win against SC Paderborn on 17 December 2014.

[161][162] It was announced on 30 January 2015 that Santana left Schalke 04 to sign for Super League Greece side Olympiacos on loan for the rest of the 2014–15 season.

[173] Having made eight appearances in all competitions, he returned to his parent club after Olympiacos did not opt to sign him on a permanent basis.

[174][175] On 11 January 2016, Santana signed a contract with the Russian Premier League side FC Kuban Krasnodar.

On 10 July 2020, it was announced that Chapecoense signed Santana until on 30 December 2020, ending his two years spell as a free agent.

[206] Having not appeared in the first team for the next three months, he made his debut for the club, starting the whole game, in a 3–1 win against Sampaio Corrêa on 20 November 2020.

When I signed with Chapecoense, they were very bad in Santa Catarina, in the sticking zone, and a rebirth of eighth started, playing against the first and becoming champion.

[218] His defensive skills and his understanding of the game on the football pitch led to comparisons with defenders Lilian Thuram,[220] Lúcio,[220] and Naldo.

[107] In November 2009, Santana and his teammate Lucas Barrios were diagnosed with H1N1 (Swine flu) virus that saw the pair being quickly vaccinated.

[225][226] In April 2014, Santana and his then teammate Sead Kolašinac were reprimanded and fined by Jens Keller and manager Horst Heldt after they were caught attending a nightclub at 3am.