Bresnan represented England at youth level, with 7 Youth Tests and 23 Youth ODIs for England U-19s. He earned his first international call-up in June 2006 when he was named in the England ODI squad to play Ireland and Sri Lanka. Bresnan made his England debut in the Twenty20 international against Sri Lanka at the Rose Bowl on 15 June 2006. He scored 6 not out and conceded 20 runs from his two overs. Two days later he appeared in his first One Day International against the same opposition at Lord’s, taking 1–44 from nine overs as England fell to a 20-run defeat.

Bresnan made his maiden first-class century in April 2007 during a County Championship match against Surrey at The Oval, beating his previous highest score of 94. During the innings, he also passed the landmark of 1,000 runs in first-class cricket. Bresnan scored 116 and in doing so, alongside Jason Gillespie, set a record ninth-wicket partnership for Yorkshire: the pair put on 246 before Bresnan was stumped off the bowling of Nayan Doshi. It was the fourth-highest ninth-wicket partnership in all first-class cricket In July Bresnan scored his second first-class ton, this time for England Lions against a touring Indian team which included Zaheer Khan, Ishant Sharma, and Sreesanth. His innings of 126 not out was a new personal best.

On 29 April 2009, nearly three years since last being involved in international cricket, Bresnan was named in the England squad for the upcoming Test series against West Indies, replacing the injured Andrew Flintoff. Seven days later Bresnan made his Test debut for England at Lord’s. He scored nine with the bat, and failed to take a wicket – being allocated only a few overs given the success of Stuart Broad, James Anderson and fellow débutant Graham Onions. In the second match, however, Bresnan picked up three wickets, including his maiden wicket of Brendan Nash and then took Denesh Ramdin two deliveries later.

England then took part in the 2010 ICC World Twenty20 and Bresnan played in all their matches, culminating with victory over Australia in the final; this was the first time England had won an ICC tournament. In the first game of the tournament, Bresnan played a limited role, not being required to bat and only bowling 1 over for 7 runs. In the second match of huge tournament he bowled two overs against Ireland, conceding only 5 runs. He was expensive against Pakistan, bowling four overs for 36 runs, but came back well against South Africa, conceding just 14 runs in the three overs he bowled.

The 2011 English cricket season began in April. Bresnan suffered a recurrence of his calf injury and as a result was ruled out of England’s three-match Test series against Sri Lanka.

Though included in England’s touring party in January 2012 for the Test series against Pakistan in the UAE Bresnan did not recover from his surgery in time to take part in the series, but did play in one of the five ODIs that followed the Tests. In this game he took figures of 1–47 and made 4 not out to help England win the match by four wickets. Next England played two Tests in Sri Lanka in March and April. After missing the first match, Bresnan played in the second at the expense of spin bowler Monty Panesar; England won the match to draw the series 1–1, protecting their status in the ICC Test Championship as the best team in the world. He picked up 2–47 in the first innings and then took 1–24 in the second, although he only made 5 runs with the bat.

In June 2020, Bresnan agreed to leave Yorkshire County Cricket Club, in a bid to play first-team cricket elsewhere to prolong his career. He joined Warwickshire on loan for the 2020 season, and signed a two year permanent deal with the club for the 2021 and 2022 seasons.