In 1982, Oshiomole became the Secretary-General of the National Union of Textile Garment and Tailoring Workers of Nigeria.
In 1999, Oshiomole while still occupying his new office, he was also elected as President of Nigeria Labour Congress (NLC), the body responsible for workers welfare in the country. Oshiomole went on with his winning streak by winning his reelection bids as the President of Nigeria Labour Congress and Secretary-General of the National Union of Textile and Garment workers simultaneously. That was awesome from a young politician who he was by then. At the end of his two terms as labor President.
in 2006, Oshiomole indicated interest to contest for the 2007 gubernatorial election of Edo state and he registered with the then Action Congress(AC) now known as the All Progressive Congress (APC). Now before his election, the state was under the ruling Peoples Democratic Party with Lucky Igbenedion being the Governor. Oshiomole’s gubernatorial ambition was seen as a herculean task of defeating the PDP candidate Senator Oserheimen Osunbor, who had the backup of the likes of President Olusegun Obasanjo, the PDP BOT Chairman Chief Anthony Anenih, the state Governor Igbenedion, and a respected High Chief Gabriel Igbenedion. But upon all these great political figures Oshiomole triumphed at the poll although he was originally declared the loser by the electoral umpire but the court acknowledged his victory in 2008 and he was sworn in as Governor of Edo state.
In 2012, Oshiomole contested for his second term in office and defeated his major contender General Charles Airhiavbere the candidate of the PDP in a landslide.
In 2016, Oshiomole has completed his eight years in office successfully. He then publicly confirmed his support for his political godson Mr. Godwin Obaseki against the ambition of his deputy Pius Odubu. In the main election, he led the campaign of Godwin Obaseki to defeat the PDP candidate Pastor Osagie Ize Iyamu who is now the current APC governorship candidate in Edo state.
In 2018, Oshiomole defeated other candidates to emerge the National Chairman of the ruling APC.
Having maintained a winning streak since 1982 Oshiomole appears to be at the verge of tasting his first defeat due to his disagreement with state Governor Godwin Obaseki whom he almost singlehandedly made governor in 2016. Following the inauguration, Oshiomole vowed that Obaseki will not win APC candidacy for the second term, while Obaseki vowed to cripple Oshiomole politically.