He made his senior and league debut on 17 April 2009 in a 4–1 home win against Al Sharjah Club, but he did not play a significant role in his debut match. His second match was against Al Dhafra on 26 April when he scored his first senior goal for Al Jazira. He started next match against rivals Al Ain in the Dubai derby. His talent emerged remarkably and he scored his second senior goal in the 90th minute and match ended 2-0 to Al Jazira. He made his AFC Champions League debut against Al Ittihad on 22 April 2009 after coming on as a late substitute. On 19 May 2009, he scored his first Asian Champions League goal in the 49th minute against Esteghlal in a 2–2 draw. Mabkhout gained momentum after his first season, receiving a reputation for creating goal scoring opportunities. He formed a prolific partnership with Ricardo Oliveira, who was his teammate from 2009 to 2014. This partnership significantly contributed towards the development of Mabkhout's talents in his formative years.
Mabkhout made his senior national team debut on 16 October 2012 at Za'abeel Stadium in Dubai against Gulf Rival Bahrain in a friendly match, Ali Mabkhout has scored his first ever hat-trick and led UAE to a massive 6–2 win.
Ali Mabkhout played in his first major senior international tournament at the 21st Arabian Gulf Cup in 2013. He was selected by UAE international team coach Mahdi Ali. He played a significant part in UAE's victory. In the group stage, against Qatar he scored in the 28th minute, in a match which ended 3–1 to UAE. He also scored a fantastic goal against Bahrain in the second group match. After qualifying from their group, UAE faced Kuwait in the semifinal, winning 1-0, before beating Iraq 2-1 in the final. This trophy was his first as a first team player.
Mabkhout was named in UAE's 23-man squad for the 2015AFC Asian Cup, held in Australia. He started the opening match of the tournament against Qatar and scored twice in 4–1 win. In the following match against Bahrain, Mabkhout scored the fastest goal ever scored in AFC Asian Cup history in the fourteenth second. UAE won the match 2–1 and qualified to the knockout stage. In the quarter-final, Mabkhout scored the opening goal of a 1–1 draw with Japan at Stadium Australia in Sydney. He went on to convert his penalty kick as the Emiratis defeated the defending champions 5–4 in a penalty shootout. He also scored the winning goal in UAE's 3–2 win over Iraq in third-place match. He then won the Golden Boot as the tournament's top goalscorer with 5 goals.