Previously, with Australia's youth sides, Wilkshire took part in the 2001 FIFA U-20 World Cup and the 2004 Summer Olympics.

Wilkshire then travelled to Canberra to spend a year at the AIS football program, Australia's elite sports academy.

After progressing through the first team,[2] Wilkshire made his Middlesbrough debut on 6 March 2002, where he played the whole game, in a 1–1 draw against Southampton.

[4] He went on to make further senior appearances for them in the Premier League, including a sending off against Arsenal,[5] and also started in an FA Cup semi-final.,[6] but ultimately never established himself in the first team.

In search of regular football, Wilkshire decided on a move to Second Division club Bristol City for an undisclosed fee.

[8] Wilkshire made his Bristol City debut, making his first start and playing 90 minutes, in a 5–0 win over Notts County in the opening game of the season.

[14] By the end of 2004, he scored six more goals, which came against Huddersfield Town,[15] Hull City,[16] MK Dons,[17] Tranmere Rovers (twice)[18] and Blackpool.

[35] After serving a two match suspension,[36] Wilkshire made his return to the first team from injury, where he assisted one of the goals, in a 2–2 draw against AZ on 17 September 2006.

[39] After suffering from a knee injury against ADO Den Haag on 28 January 2007,[40] which saw him out for weeks, he made his return to the first team, coming on as a substitute in the second half, in a 0–0 draw against Willem II on 24 February 2007.

[57] Wilkshire became a first team regular at the club and finished his first full season, making eleven appearances and scoring two times in all competitions.

[61] Despite this, Wilkshire continued to be in the first team regular following his sending off and went on to finish the season, making thirty-two appearances in all competitions.

In the 2011–12 season, Wilkshire began to play in the right-back position and his performance against Kuban Krasnodar, which saw them win 1–0 on 9 April 2011, earned him Team of the Week.

[66] His performance attracted interests from league's rivals and bigger spender Anzhi Makhachkala in the summer transfer window, but the move never happened.

[79] On 31 July 2014, Wilkshire signed a one-year deal with Dutch Eredivisie side Feyenoord on a free transfer.

[82] Wilkshire then played a role when he set up a goal three times this season, including one with a 1–0 win over NAC Breda on 21 December 2014.

[85][86] His last appearance came on 19 February 2015 in a UEFA Europa League match against Roma, where he played for 30 minutes before suffering a hamstring injury, resulting him being substituted, in a 1–1 draw.

[91] On 18 November 2015, Wilkshire signed a one-year contract, with the option of an additional year, with Russian club Terek Gronzny, beginning on 1 January 2016.

[94] In his sixth appearance for the club, however, Wilkshire received a red card after a second bookable offence, in a 1–0 loss against CSKA Moscow on 7 May 2016.

[102] In July, 2017 Wilkshire returned to Australian club football, signing a one-year contract with Sydney FC as an injury replacement player for Rhyan Grant.

[103] Wilkshire scored his first goal for the Sky Blues in a 1–0 win over Melbourne City in the Round 5 of the A-League season, lofting the ball over the keeper on the volley from a Michael Zullo cross.

[104] Wilkshire scored the club's first goal in the 2018 AFC Champions League, blasting home a parried shot away to Shanghai Shenhua at Hongkou Football Stadium.

[106] At the end of the 2018 National Premier Leagues season, Wilkshire retired from playing football and took up a position as Wolves' head coach.

[107] Wilkshire has represented Australia at youth level earlier in his career, playing in the 2001 FIFA U-20 World Cup in Argentina,[108] and in the 2004 Athens Olympic Games,[13] where he once captained the side against Iraq.

[110] During three years of playing regular first-team football for Bristol City, Wilkshire's game and versatility improved; so much so that former Australia coach, Guus Hiddink, described him as a "modern player."

He was then involved in the second goal in the 82nd minute putting a left-footed ball over the Omani defence to set David Carney free who then crossed to Brett Emerton who scored to win the game 2–1 for Australia.

Late in Australia's last game versus Serbia, Wilkshire injured his groin and was subbed off – the severity of the injury has not been made public.