Season 12
Reilly first appeared on Big Brother in its twelfth season, aired in the summer of 2010. Within the first week of the season, Reilly entered into a romantic relationship with fellow houseguest Brendon Villegas, leading to the pair becoming immediate targets. Despite being nominated in the first week, Reilly was spared when the rest of the house decided fellow nominee Annie Whittington was a bigger threat.
Reilly won two Head of Household competitions during her stay in the house, in the second and fourth weeks, resulting in the evictions of Monet Stunson and Kristen Bitting. Reilly was known for her many feuds during her stay, most notably with Ragan Fox and Britney Haynes. Eventually, Reilly and Villegas were nominated together in the fifth week of the season. Despite Villegas' attempts to get the other players to keep Reilly instead of him, Reilly was evicted unanimously. Reilly later returned to the house as a guest for one day as part of the "Pandora's Box" twist. As a result of her ninth-place finish, Reilly became the first member of the Big Brother 12 jury, and eventually voted for runner-up Lane Elenburg to win the $500,000 prize.
Season 13
One year later, Reilly and Villegas (by then her fiancé) returned to Big Brother for its thirteenth season, as part of a "Returning Duos" twist. Reilly claimed she was returning to the show in a bid to redeem herself following her previous appearance. Reilly and Villegas quickly forged an alliance with the four other returning players, father and daughter, Dick and Daniele Donato of Big Brother 8 and fellow couple, Jordan Lloyd and Jeff Schroeder of Big Brother 11, as well as a side alliance with Porsche Briggs. The alliance, known as "the Veterans," dominated the house in the early weeks, with Reilly winning Head of Household (HoH) in the first and third weeks, as well as the Power of Veto in a two-person challenge with Villegas in the first week.
The alliance fell apart in the second of Reilly's HoH weeks, when Daniele was caught in her attempts to turn the two couples against each other. However, Daniele then proceeded to win the next HoH competition, nominating Reilly and Villegas against each other, sparking a long-running feud between the two women. After winning the Power of Veto, Villegas decided to use it on Reilly, effectively ensuring his own eviction. Reilly was nominated again the following week, but was spared when confusion about an upcoming twist caused Lawon Exum to volunteer to be evicted in her place, in the mistaken belief that it would give him an advantage in the game. In reality, the evicted player and the winner of an America's Choice vote would compete to return, with Villegas winning the vote and then beating Exum in the subsequent competition, regaining his place in the game. His stay was short lived however, as he was evicted at the hands of Donato once again a week later.
Reilly took revenge the following week, evicting Daniele after finding herself as the swing-vote. After narrowly surviving an eviction vote 3–2 against Schroeder, Reilly paired with Lloyd when the duos twist briefly returned, and won a key Veto competition that kept them both in the game at the expense of Shelly Moore. Reilly then followed up by winning HoH for the third time, resulting in the eviction of Kalia Booker. After failing to win the final Veto competition, Reilly reformed her early alliance with Briggs, and the pair worked together to make the final two, with Briggs evicting Lloyd in the final four stage, and then Reilly evicting Adam Poch the following week after she won HoH for the fourth time.
Reilly was crowned the winner of Big Brother 13 in a vote of 4–3 over Briggs, earning the jury votes of Villegas, Schroeder, Lloyd and Moore, and losing the votes of Donato, Booker and Poch. Reilly won $500,000 for winning the show.