[15] Kevin O'Brien represented Ireland in the Under-19s World Cup of 2004 in which he made 241 runs to help his country reach the Plate Semi-Final before being defeated by Australia Under-19s.

[16] In June 2006, he made his One Day International debut in Ireland's inaugural ODI game, against England in Belfast.

In their second game of the tournament, against Bermuda, O'Brien took his career best figures of 2 for 38 by taking the wickets of middle order batsmen David Hemp and Lionel Cann.

In the chase he made 54, his maiden ODI half century and helped his side win with 8 balls to spare.

Ireland then took on Canada and O'Brien continued his good form with the bat by making his 3rd consecutive score of fifty plus with a composed 52.

The next tour for O'Brien was the 2007 World Cup in the Caribbean and it would be his biggest test yet as 6 of his 7 One Day International games prior had been against non-Test playing nations.

His first ball was a full toss but Zimbabwean captain Prosper Utseya hit it straight to Eoin Morgan at cover to give him his first World Cup wicket.

Ireland came up against Pakistan in the next game and they restricted the Test nation to just 132 with O'Brien taking the wicket of Shoaib Malik.

Arguably his best performance of the World Cup was his fast 48 runs scored against Bangladesh which helped secure a historic Irish victory.

The previous season O'Brien had scored 93 against the club, impressing Mick Newell, Nottinghamshire's director of cricket.

In their second match against Canada, O'Brien finished with 0–38 in the Canadian innings, and 5 off 2 balls with the bat as Ireland narrowly lost by 4 runs.

[31] On 2 March O'Brien hit the fastest century in World Cup history, off just 50 balls against England helping his team to successfully chase down a target of 328 when at one stage they were struggling at 111/5.

On 23 May 2013, at Clontarf Cricket Club Ground, Dublin, he scored an unbeaten 84 in 47 balls against Pakistan which helped Ireland to tie the match.

Ireland required 15 runs in the last over to win the match, O'Brien hit last ball of Saeed Ajmal to boundary to pull out a thrilling 'tie' for the Irish team.

[36] John Bracewell, Gloucestershire's coach, viewed O'Brien as primarily a one-day player and believed his style of batting was best suited to situations where the team needed to increase their run-rate.

[38] His innings of 119 runs against Middlesex came from 52 deliveries and helped lift Gloucestershire to the highest total in the history of domestic T20 cricket.

O'Brien shared an opening stand of 192 with Hamish Marshall, who also scored a century, and the pair set a record partnership for any wicket in the format.

[45][46] After the internationals O'Brien returned to Gloucestershire, and again helped his team to victory over Middlesex, this time scoring 58 not out from 35 balls.

[47] Gloucestershire finished the Friend's Life t20 competition with four wins from sixteen matches, leaving them 8th out of nine teams in their group.

With regular captain William Porterfield playing for Warwickshire and Trent Johnston who often stood in injured, O'Brien was chosen to lead Ireland against Namibia.

[63][64] In September 2019, he was named in Ireland's squad for the 2019 ICC T20 World Cup Qualifier tournament in the United Arab Emirates.

[66] Later the same month, during the 2019–20 Oman Pentangular Series, O'Brien became the first batsman for Ireland to score a century in a T20I match, when he made 124 against Hong Kong.