After a three-year absence, Balfour made his return to the major leagues on 18 July, 2007, in the 8th inning with the Milwaukee Brewers.

[2] The Brewers designated Balfour for assignment on 27 July 2007, and traded him to the Tampa Bay Rays that day for Seth McClung.

[7] He earned a save on 31 May against the Chicago White Sox, retiring Brian Anderson to end the game in a Rays 2–0 win.

[8] In a series sweep against the Chicago Cubs at Tropicana Field, he was credited with two of the three wins – the first on 16 June, relieving Scott Kazmir with the score 1–1 and bases loaded, pitching 1+1⁄3 perfect innings in a 3–2 win;[9] the second on 18 June, entering the game trailing 1–2, and pitching 1+2⁄3 innings, recording three strikeouts, in a game the Rays won 8–3.

On 2 October 2008, during Game 1 of the ALDS, he was involved in an exchange of words with Chicago White Sox shortstop Orlando Cabrera.

[17] On 8 July 2013, Balfour set the record for most consecutive saves for the Athletics, earning his 41st in a 2–1 win over the Pittsburgh Pirates.

[19] In 65 appearances, Balfour finished the year 38–41 in save opportunities, going 1–3 with a 2.59 ERA as the team's closer, striking out 72 in 62.2 innings with a .206 OBA.

In Game 3 of the 2013 ALDS against the Detroit Tigers, Balfour began cursing at Victor Martinez, who then answered back, leading to both benches clearing.

Balfour claimed that Martinez gave him a "viral death stare" prior to exchanging words as he composed it on Twitter.

[23] Balfour responded that he was perfectly healthy and other doctors who examined him disputed the Orioles interpretation of his physical results.

[29] While pitching with Triple-A Durham, Balfour held a 2.79 ERA in eight games, owning an 11:4 K:BB ratio over 9+2⁄3 innings.

[31] Balfour's father, David, was a rugby player and general manager and owner of the Sydney Blue Sox.